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ABSTRACT
Year : 2014  |  Volume : 1  |  Issue : 2  |  Page : 115-137

2nd World Congress on Ovulation Induction and Ovarian Stimulation Protocols Jaipur Marriott, Rajasthan, India, 7th to 10th August 2014


Date of Web Publication4-Sep-2014

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How to cite this article:
. 2nd World Congress on Ovulation Induction and Ovarian Stimulation Protocols Jaipur Marriott, Rajasthan, India, 7th to 10th August 2014. IVF Lite 2014;1:115-37

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. 2nd World Congress on Ovulation Induction and Ovarian Stimulation Protocols Jaipur Marriott, Rajasthan, India, 7th to 10th August 2014. IVF Lite [serial online] 2014 [cited 2022 Jan 18];1:115-37. Available from: http://www.ivflite.org/text.asp?2014/1/2/115/140133

8th August 2014


  Why 'more is less and less is more? Top


Zeev Blumenfeld

Department of Reproductive Endocrinology, Rambam Medical Centre, Haifa, Israel, E-mail: bzeev@tx.technion.ac.il

Mild ovarian stimulation protocols for in vitro fertilization (IVF) minimize ovarian hyperstimulation syndrome and multiple gestations without compromising PR. What is the putative explanation to the improved outcome of the soft, controlled ovarian stimulation (COS) or why "Less is more?" At least four possible mechanisms can be put forward to explain this apparent paradox:

  1. Natural selection: "Quality for Quantity".
  2. Early gestation high estradiol (E 2 ) effect on fetal growth
  3. Better intra follicular hormonal milieu.
  4. The growth hormone (GH)/IGF's/GH-binding protein (BP).


  1. In the natural cycle of spontaneous folliculogenesis, the best and healthiest follicle which will ultimately ovulate is selected by the principle of "Quality for Quantity." Out of 700-1000 primordial follicles which start the long journey of folliculogenesis, lasting somewhere between 4 and 9 months, only one usually ovulates. Thus, nature eliminates the less than ideal follicles with aneupoidy or other suboptimal genetic, hormonal, or growth factors stimulation, enabling for continuation of species by the best ova. Indeed petroleum geo-services has demonstrated that milder ovarian stimulation for IVF reduces aneuploidy in the human preimplantation embryo.
  2. High maternal E 2 environment in the first trimester is correlated with increased risks of low birth weight (LBW) and small-for-gestational age (SGA). High concentrations of E 2 in the late follicular phase of IVF cycles correlate with high E 2 levels in the generated gestations at 4 and 8 weeks and significantly correlated with higher rates of SGA and LBW neonates versus spontaneous pregnancies or those generated by embryo transfer of thawed embryo.
  3. Is the steroid hormone profile in FF different in naturally matured follicles, (natural cycle, natural cycle in vitro fertilization [NC-IVF]), compared with COS IVF? Indeed, antiMüllerian hormone, LH, testosterone, E 2 , and androstenedione are significantly higher, in NC-IVF than in stimulated-IVF follicles, suggesting an alteration of the follicular metabolism in stimulated IVF cycles as a possible mechanism of suboptimal outcome.
  4. Normal folliculogenesis is stimulated by FSH synergistically with IGF's. The ovarian effect of GH is to increase the IGF's levels and augment folliculogenesis. The GH in plasma is bound to GH-binding protein (GH-BP) which is increased by E 2 . It has been suggested that high supraphysiologic levels of E 2 [>6000 pM] my increase GH-BP to very high levels which may bioneutralize GH and diminish the resultant IGF levels, necessary for optimal synergism with FSH.



  Ovarian Torsion As A Complication Of Ovarian Hyperstimulation Syndrom Top


Vishakha Munjal

Department of Obstetrics and Gynaecology, Moolchand Medcity, Delhi, India, E-mail: drvishakhamunjal@yahoo.com

The incidence of ovarian torsion is increased during controlled ovarian hyperstimulation. This presentation is about a case of polycystic ovarian disease with ovarian hyperstimulation syndrome who had exercise induced bilateral ovarian torsion in the following cycle and was managed laparoscopically. This case report suggests that:

  1. Ovarian torsion should be high in the differential diagnosis in patients experiencing severe abdominal pain with a history of recent gonadotrophin stimulation.
  2. The risk of ovarian torsion persists beyond the treatment cycle and that patients should be instructed to refrain from exercise or strenuous activity if regression to normal ovarian size has not been documented.
  3. Ultrasound is the diagnostic modality of choice. Doppler has no additional advantage.
  4. Immediate laparoscopy and detorsion is the treatment of choice.
  5. Missing the diagnosis means losing the ovary which is a high price to pay in infertility patients.
  6. Even if all the tests are negative, but there is clinical suspicion, immediate laparoscopy is the answer as there is no single test that can definitively "rule in" or "rule out" ovarian torsion.



  Mild Ovar An Stimulation And Financial Implications Top


Varsha Paidunghat

Department of Obstetrics and Gynaecology, Bombay Hospital Institute of Medical Sciences and Research, Mumbai, India, E-mail: varshapaidhungat@yahoo.com

Ovarian hyperstimulation has been an right issue from the early days of gonadotrophin-releasing hormone (GnRH) use. In an attempt to improve success rates of Intrauterine insemination and in vitro fertilization, a large no of follicles were recruited. This led to major financial implications in the form of increased cost of drugs, cost of ovarian hyperstimulation and finally the cost of multiple pregnancies. Mild stimulation attempts to alleviate these issues. By attempting for mono or bi follicular growth, the need for high dose of GnRH is avoided. Consequently, this leads to a reduced incidence of multiple pregnancies. As we all know multiple pregnancies is a big drain on the pocket. And God help those where there is prematurity involved. Finally, the incidence of ovarian hyperstimulation syndrome is reduced with lesser need for hospitalization, lesser loss of working days and lesser need for special care. Mild ovarian stimulation is not only patient friendly but also pocket friendly.


  Recombinant Luteinizing Hormone (Lh) Versus Human Menopausal Gonadotrophins For Lh Activity Supplementation Top


Shweta Kaul Jha

Gk Fertility and IVF Centre, Indore, Madhya Pradesh, India, E-mail: drshwetakauljha@gmail.com

In the normal and stimulated menstrual cycles follicle-stimulating hormone (FSH) and luteinizing hormone (LH), play essential roles in the development of the ovarian follicles as well as in the proliferation of the endometrium. FSH receptors are expressed only at the granulosa cells while LH receptors are expressed in both theca and granulosa cells. FSH is the main regulator of antral follicular growth but optimal follicular development occurs within an "LH window", above a certain "LH threshold" and below an "LH ceiling". The general consensus regarding LH supplementation is that most women undergoing controlled ovarian stimulation (COS) have sufficient levels of endogenous LH and do not require supplementation. However, a subgroup comprising 15-20% of these women have less sensitive ovaries which includes the categories of older patients (≥35 years), poor and slow/hypo responders to COS, and those with deeply suppressed endogenous LH that might benefit from LH supplementation but there is currently no consensus on the most suitable LH activity supplementation. About LH-containing gonadotropin, preparations are available in the market, are, human menopausal gonadotrophins and recombinant LH (rec-hLH) with there advantages and disadvantages. Larger Randomized controlled trials are required to determine if one preparation is superior over other and what is the optimal dose and timing of LH supplementation.


  Luteal Support Post Agonist Trigger For Ovarian Hyperstimulation Syndrome Prevention: The Introduction Of 'Luteal Coasting' As A Novel Approach Top


Shahar Kol

IVF Unit, Rambam Health Care Campus, Israel Institute of Technology, Haifa, Israel, E-mail: skol@rambam.health.gov.il

In recent years agonist trigger has become a viable alternative for the conventional human chorionic gonadotropin (hCG) trigger, especially in the context of ovarian hyperstimulation syndrome (OHSS) prevention. Agonist trigger is now routinely used in egg donors. A recent survey indicates that in Europe as many as 36% of in vitro fertilization cycles are triggered with agonists. Agonist trigger causes a quick and irreversible luteolysis, therefore, in fresh cycles luteal support is mandatory. The concept of "tailored", ovarian response-based luteal support was developed. For normal responders (<14 follicles of >11 mm) one bolus of 1500 hCG on the day of oocyte retrieval will yield excellent clinical outcome (Humaidan). In "moderate" high responders (15-25 follicles of >11 mm), a single bolus of 1500 hCG on the time of oocyte retrieval will result is excellent clinical outcome with reduced OHSS risk. In patients with >25 follicles >11 mm, the options so far included "freeze all" (Devroey), or intensive E2+P- based luteal support (Engman). The above strategies took into account the cycle specific ovarian response as the only factor on which to base the decision how to "tailor" the luteal support. In addition, a fixed time points were preset for hCG delivery: Dual trigger (Engman), on the day of oocyte retrieval (Humaidan), or 3 days post oocyte retrieval (Haas). Post agonist trigger P level returns to baseline 5-6 days post agonist trigger, explaining OHSS prevention and the early menses that follows. To further individualize luteal phase support post agonist trigger, the same principle that holds for follicular coasting, used in the context of OHSS prevention, may be valid. In other words, monitoring daily P levels from the day of oocyte retrieval, and administer a bolus of hCG when P level drops below a certain cutoff level. Two case reports using this strategy will be presented. To the best of my knowledge, such an approach was never described before.


  The Role Of Luteinizing Hormone (Lh) Monitoring And Lh Therapy In Controlled Ovarian Hyperstimulation Top


Rutvij Dalal

E-mail: rutvij.dalal@gmail.com

The follicular phase features a series of sequential actions of hormones and autocrine-paracrine peptides on the follicle, leading the follicle destined to ovulate through a period of initial growth from a primordial follicle through the stages of preantral, antral and preovulatory follicle. As described in the classic "two-cells-two-gonadotrophin" theory, luteinizing hormone (LH) is needed to provide the granulosa cells with androgen precursors for estradiol biosynthesis. Follicle-stimulating hormone alone can induce follicle growth, but without LH, estradiol levels remain low and pregnancy will not occur. Concept of a "therapeutic window" of LH with both a "threshold" and "ceiling" effect for successful conception in assisted reproductive technology and ovulation induction has been well characterized. There is a lot of debate surrounding whether LH monitoring during an in vitro fertilization hyperstimulation cycle really improves pregnancy rates. Blood levels of LH might not accurately determine the biologically available form. Moreover, LH is secreted in pulses, and there may be a need to monitor it serially, in order for it to be reliable. Many studies found no benefit in terms of clinical pregnancy rates and live birth rates when LH monitoring was done compared to those with no monitoring. LH levels might be assessed in a case to case basis is there is a doubt of a premature surge. Otherwise, it may increase the cost of the cycle without any significant benefit. There is no debate about the need for both hormones in women with hypogonadotropic hypogonadism, but there is significant disagreement about the need for LH in "endocrinologically normal" women. It has been shown that low-dose stimulation with low-dose LH enhances steroidogenesis without inhibiting cell proliferation whereas high dose LH suppresses granulosa proliferation initiates atresia of immature follicles and premature luteinization of preovulatory follicles. Although LH is required during follicular stimulation to provide the androgenic pro-hormones that get aromatized by granulosa cells into estradiol, it has been shown that even <1% of LH receptor activity is enough to generate optimal follicular growth. The 2010 Cochrane meta-analysis involving 14 trials did not find any significant increase in pregnancy rates, but showed a beneficial trend with recombinant LH, with respect to pregnancy loss and poor responders. To identify the specific subset of patients that might benefit from LH administration remains the clinician's biggest challenge.


  Sildenafil citrate vaginally for refractory thin endometrium Top


Purnima Nadkarni

Nadkarni Hospital and Test Tube Baby Center and 21 st Century Group of Hospitals, Gujarat, India,

E-mail: hospital21st@rediffmail.com

Despite the improvement in ovarian stimulation protocols and subsequent access to a number of dominant follicles, mature oocytes, and embryos for transfer, in vitro fertilization has successfully reached a plateau. Therefore, more attention is now a days focused on implantation and endometrial receptivity. Implantation remains a major limiting step of assisted reproductive technology (ART), and uterine receptivity is essential for successful implantation in all species. Successful implantation requires good embryo quality, appropriately timed and arranged endometrial receptivity and efficient crosstalk between the embryo and the receptive endometrium. It is thought that the impairment of any one of these factors or biological processes may result in implantation failure. The endometrium is normally a nonreceptive environment for an embryo, except during the window. Implantation window is a period during which the endometrium is optimally receptive to implanting blastocyst within the cycle days 20 and 24. Endometrial receptivity during the implantation window depends on the following factors.

Morphological markers

  1. Endometrial thickness.
  2. Endometrial echogenic pattern.
  3. Endometrial and sub endometrial blood flows.
  4. During implantation window, the endometrial epithelium encompasses four cell types: Microvilli-rich cells, pinopode cells, vesiculated cells, and ciliated cells.


Biochemical markers

  1. Endometrial adhesion molecules.
  2. Endometrial antiadhesion molecules.
  3. Endometrial cytokines.
  4. Growth factors.
  5. Endometrial immune markers.
  6. Endometrial glycodelin.
  7. Insulin like growth factor.
  8. Leukemia inhibitory factor.


The process of embryo implantation is described as having three phases

  1. Apposition: "Unstable adhesion" of the transferred embryo to the surface of the uterine lining.
  2. Attachment (adhesion): "Stable adhesion," believed to involve signaling back and forth between the embryo and the lining.
  3. Penetration (invasion): Invasion of the trophectoderm cells from the embryo through the surface of the lining deeper the stroma of the uterine lining, forming a vascular connection to the mother.


Causes of thin endometrium

  1. Permanent damage to the basal endometrium.
  2. Endometrial resistance to estrogen.
  3. Reduced blood flow.
  4. Over-exposure to testosterone.


Estrogen induced endometrial proliferation is in large part dependent upon blood flow to the basal endometrium.

Pathophysiologic status of thin endometrium

  • High blood flow impedance of uterine radial artery.
  • Poor epithelial growth.
  • Decreased vascularendothelial growth factor (VEGF) expression.
  • Poor vascular development.


A thin endometrium (<8 mm measured by ultrasound scan) has a negative impact on the success of ART. Live births are possible despite thin endometria, but the pregnancy rate among these women is poor (Dix 2010). Currently, there is a marked interest in the study of the role that the endometrium plays in the success of ART (Casper 2011; Senturk 2008).

Various treatment options available to improve endometrium quality

  • To develop ovarian stimulation protocols, that cause a minimum reduction in endometrial receptivity.
  • Exogenic 17-Estradiol.
  • Avoid clomiphene citrate which impairs endometrial receptivity and fetal development.
  • Cabergolin if hyperprolactinemia.


To improve uterine vascularization:

  • Low dose Aspirin.
  • L-arginine (Nitric oxide donor).
  • Sildenafil.
  • GnRH-agonist and granulocyte-colony stimulating factor etc.


How to Improve Endometrium receptivity and thickness by Sildenafil?

  • Sildenafil citrate-A type 5-specific phosphodiesterase inhibito augments the vasodilatory effects of NO.
  • Sildenafil citrate is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 that prevents the breakdown of cGMP and potentiates the effect of nitric oxide on vascular smooth muscles. Sildenafil citrate could lead to an improvement in uterine blood flow and in conjunction with estrogen, led to the estrogen-induced proliferation of the endometrial lining.
  • Sildenafil citrate enhances uterine blood flow and increases endometrial thickening. The achieved implantation depends on the blastocyst's ability to infiltrate the endometrium and develop a sustaining blood supply, which requires the following genes to produce the necessary proteins for digesting the endometrial cellular matrix, to regulate cell growth, and to induce angiogenesis:


  • Tumor suppressor factor (p53).
  • Plasminogen activator inhibitor 1.
  • VEGF.
  • Sildenafil citrate was enhanced markedly in p53 and stimulated angiogenic responses with increased VEGF.


Vaginal sildenafil citrate (Viagra, Pfizer, Inc., New York, NY) has been shown to be useful in increasing endometrial thickness and achieving pregnancy in women with varied uterine disorders. Various studies in the literature show that the Vaginal sildenafil (at a dosage of 25 mg, 4 times a day for 3-10 days) improves uterine artery blood flow and sonographic endometrial thickness. In this lectures, various studies to improve refractory thin endometrium have been described.


  Optimizing the gnrha trigger to improve ovulation Top


Pratik Tambe

Nirmiti Fertility and IVF, Thane, Maharashtra, India,

E-mail: drpratiktambe@gmail.com

Ovulation triggering has been the scope of much debate in the past few years. Human chorionic gonadotropin (hCG) has been the gold standard for ovulation induction as a surrogate for mid-cycle luteinizing hormone since several decades. With the introduction of gonadotrophinreleasing hormone (GnRH) antagonist protocols, it is now possible to trigger final oocyte maturation with a single bolus of GnRH agonist (GnRHa) as an alternative to hCG. Although the GnRHa induced surge effectively stimulates ovulation and oocyte maturation, differences exist regarding the duration and profile of the GnRHa induced surge of gonadotrophins when compared with that of the natural cycle. The physiology of ovulation, the mechanism of action, cascade of events following the ovulation trigger and the ultimate impact on the treatment cycle, oocyte quality and results will be discussed. In addition, the place of different trigger methods in various types of assisted reproductive technologies protocols will be elucidated. The evidence supporting the various methodologies will be highlighted. The optimization of the trigger and modifications required to prevent ovarian hyperstimulation syndrome and their success will be explained.


  Identification of patients at high risk for excessive response to ovarian stimulation Top


Ofer Fainaru

Department of Obstetrics and Gynaecology, IVF Unit, Hillel Yaffe Medical Center, Hadera, Israel, E-mail: ofainaru@techunix.technion.ac.il

The basis for individualization of treatment in patients undergoing in vitro fertilization is a prediction of the ovarian response to gonadotropin stimulation, forecasting poor, normal or high response. Clinicians may then choose between various treatment strategies to maximize efficacy and safety in a different response categories. Hyper-responders are usually defined as women with high numbers of oocytes retrieved following a standard protocol of controlled ovarian stimulation. Although these patients are generally considered a good-prognosis group, it is currently debated whether a high ovarian response is associated with decreased chance of a successful outcome as compared with a normal response. Furthermore, severe ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of multifollicular ovarian stimulation. Therefore, it is important to identify these high-risk patients before the onset of gonadotropins. Factors associated with hyper-response include patient history, the presence of polycystic ovary syndrome (PCOS), younger age and lower body mass index. Of these, the most important clinical predictor of severe OHSS is PCOS. Studies of endocrine, follicular and ovarian reserve tests have given disappointing results. Estradiol (E 2 ) is the best-defined endocrine predictor for OHSS as the cascade of events that leads to the development of OHSS is almost always accompanied by elevated E 2 levels. Among dynamic tests, neither the exogenous follicle-stimulating hormone ovarian reserve test (EFORT) nor the clomiphene citrate challenge test is adequate alone to predict hyper-response. The inhibin B increment in the EFORT is the best predictor, but with limited accuracy. Anti-Mullerian hormone (AMH) may also be a marker for patients at risk for OHSS. Baseline pretreatment serum levels of AMH in patients who experienced OHSS were found to be 6-fold higher than in normal age-and weight-matched controls. AMH could be the first serum marker of ovarian response that can be measured on any day of the menstrual cycle. Many other potential predictors of hyper-response have been investigated, such as total ovarian volume, interleukin-10, vascular endothelial growth factor and inhibins. However, their clinical value has not been proven as they do not clearly discriminate between normal and hyper-responders.


  Role of vitamin d in impaired fertility treatment Top


Namita Kotia

Aastha Fertility Care, Jaipur, India,

E-mail: namitakotia2000@yahoo.co.in

Aim: To assess and evaluate the relationship between Vitamin D and fertility in women and men. Methods: Systemic literature search and study. Results and Discussion: Vitamin D is a fat soluble steroid hormone having endocrine, paracrine and autocrine functions. Vitamin D receptors and Vitamin D metabolizing enzymes are found in reproductive tissues of male and female, keeping action of Vitamin D not unique to skeletal system but a definitive role in polycystic ovary syndrome, impaired fertility, endometriosis, impaired anti-müllerian hormone, and impaired semen parameters.


  Myomectomy before in vitro fertilization: which fibroids need to be removed Top


Kishore Pandit

Department of Obstetrics and Gynaecology, AIMS Hospital and Research Centre, Pune, India, E-mail: drkspandit@gmail

The decision to do a Myomectomy before an in vitro fertilization (IVF) cycle is not an easy one. You will always be faced with the "Do you think it is essential, doctor?" question. To answer this question you have to have clear-cut evidence that this woman will not get pregnant following an IVF cycle-except if she had a Myomectomy. Or if she gets pregnant, she will probably lose her baby because of the fibroids her uterus carries. We have to deploy proper judgment in each individual case based on the age, as well as, the number and size of the intramural myomas. A single myoma of 4 cm size or less that is not encroaching on the cavity in a woman in her late thirties may deserve a single trial to get pregnant through IVF without Myomectomy. If that fails or ends in miscarriage, she may be counseled for surgery before the second trial. However, larger and multiple myomas, especially in a younger patient may deserve surgery before enrolling her in her first IVF cycle. Single sub-serousmyomas of sizes <5 cm may well be ignored, and the patient is allowed to go through IVF. However, if larger or associated with intramural myoma, surgery may be considered prior to enrolling her in an IVF cycle.


  Improving intrauterine insemination pregnancy rates Top


Gulam Bahadur

Department of Obstetrics and Gynaecology, NHS Trust Hospitals, UK, E-mail: bahadur.g@gmail.com

Therapeutic intrauterine insemination (IUI) using the husband's sperm is commonly performed for malefactor infertility, as well as to enhance the probability of conception in various infertility conditions IUI is the most universally practiced procedure in sub fertility treatment. The European in vitro fertilization Monitoring Program in 2004 reported 98 388 IUI cycles from 19 countries leading to 12 081 births (12.3%/cycle), of which 87% were singleton, and 13% were multiple births (Andersen et al., 2008). Some investigators have questioned the value of IUI for couples about sperm concentration. Confine et al. reported the lowest total motile sperm count at which pregnancy occurs ranges between 1 and 5 × 10 6 sperm. In contrast Brasch et al. found that there was a significantly increased chance for pregnancy whenever the total motile sperm count used for IUI exceeded 20 × 10 6 spermatozoa. The majority of studies attempting to find which sperm characteristics correlated with cycle outcome included multiple female infertility problems. Thus, the results might be biased by the other infertility etiologies that were treated in parallel. The aim of this presentation is to reflect on our experience of improving IUI outcomes while reviewing areas which can improve outcomes and our understanding of patient management to give better results. Unique data will be presented at the meeting which will reaffirm confidence in the IUI procedures and to obviate unnecessarily expensive procedures.


  Granulocyte colony stimulation factor in refractory thin endometrium Top


Anirudh Singh

Dr. Singh Test Tube Baby Centre, Meerut, India,

E-mail: dr.anirudh@sify.com

Chronically thin endometrium resistant to standard treatments affects a small number of patients undergoing in vitro fertilization (IVF). This problem, nevertheless, is of considerable importance because endometrium below 7 mm in thickness is widely considered sub-optimal for transfer and associated with reduced pregnancy chances. Various remedies have been proposed, including extended estrogen administration if time allows, low-dose aspirin and treatment with pentoxifylline and tocopherol and with vaginal sildenafil citrate. However, even utilizing these remedies, a small number of women remain unresponsive. A growth spurt in endometrial thickness can be observed within 48 h of granulocyte colony stimulation factor (G-CSF) administration. How G-CSF accomplishes this is, however, unknown. Surprisingly, little is known about how G-CSF impacts on the endometrium. G-CSF is a glycoprotein with growth factor and cytokine functions and is produced in different tissues/cells, including endothelium, macrophages and in other immunocytes. In the central nervous system, G-CSF not only acts as a proliferant by inducing neurogenesis but also has anti-apoptotic functions. It, therefore, has been proposed as a potential therapeutic agent in neurodegenerative diseases. Investigating the effect of G-CSF on proliferation and differentiation of normal human endometrial stromal cells, concluded that G-CSF enhances cAMP-mediated decidualization of human endometrial stromal cells in both an autocrine and paracrine fashion. Macrophage (M)-CSF enhances G-CSF secretion from unstimulated human endometrial stromal cells but not from 8-BR-cAMP-stimulated cells. Among other cytokines and chemokines, G-CSF and granulocyte-macrophage CSF (GM-CSF) are secreted apically in polarized epithelial cells. It is unknown how G-CSF achieves the rapid proliferation of endometrial architecture.


  In vitro maturation of oocytes results are comparable and may have advantages over standard in vitro fertilization Top


Adrian Ellenbogen

Department of Obstetrics and Gynaecology, IVF Unit, Hillel Yaffe Medical Center, Hadera, Technion, Haifa, Israel,

E-mail: ellenbogen55@yahoo.com

Introduction: In vitro maturation (IVM) has advanced significantly from its initial description to its current widespread clinical applications. Despite these advances, however, there are still many controversial issues surrounding this treatment. Given that IVM is an emerging protocol (at least in humans), there are many controversial areas of debate, and especially regarding the subject of the best candidates for IVM; how should we select our patients? Aims: To evaluate the outcome of IVM procedure in perspective with known routine IVF results. Settings and Design: University IVF Unit. Materials and Methods: The PubMed database was searched from 1999 to 2013 for publications concerning the indications and results of IVM and to examine the possibility that IVM results may be comparable to standard IVF. Results : In vitro maturation (IVM) of the oocyte procedure obtained a 35% clinical pregnancy rate in young women, comparable with in vitro fertilization (IVF) in many programs. The IVM obstetrics and perinatal outcome are comparable with IVF/intracytoplasmic sperm injection. The improvement in treatment and protocol has produced good results. Conclusions: In vitro maturation of oocytes is a simple procedure. It is economical and less stressful for women. Puncture is simple and safe. It can avoid short-term complications, such as ovarian hyperstimulation syndrome and long-term complications, such as hormone dependent neoplasms including breast and ovarian cancers. Studies to date have not identified an alarming rate of congenital anomalies in IVM children. IVM holds great promise as an alternative to assisted reproductive technologies and may be the procedure of choice not only for infertile patients but also for obtaining oocytes for donation or fertility preservation. Improving embryonic-endometrial synchrony through pharmaceutical or other manipulation of endometrial/uterine receptivity will hopefully result in future improvements in IVM success rates.


  Current methods of improving endometrial receptivity Top


Pallavi Satarkar

Anant IVF Center, Baroda, E-mail: pallavisatarkar@yahoo.com

Introduction

  • Since the introduction of in vitro fertilization, several innovations have made ovulation induction, oocyte retrieval, fertilization capability and embryonic development more efficient. However, lacunae still exist in our understanding of the implantation process.
  • Uterine receptivity is defined as a restricted time-related period when the uterus is receptive to blastocyst attachment and implantation.
  • Practical limitations in the evaluation and improvement of uterine receptivity may play a determining role in the establishment of uterine receptivity for implantation since the events of implantation are regulated by a complex morphological and biochemical change in the endometrium.


Strategies for improving endometrial receptivity

  • To develop ovarian stimulation protocols that cause a minimum reduction in endometrial receptivity or increases it.
  • To avoid the Embryo transfer during the stimulation cycle altogether by freezing embryos and replacing them in subsequent cycles.
  • To improve uterine vascularization.
  • To treat the pathological conditions.


Various agents and procedure known to increase implantation

  • Intravenous Immunoglobullins (IVIg).
  • Intralipid.
  • Allogeneic lymphocyte therapy.
  • Recombinant human leukemia inhibitory factor.
  • Acupuncture.
  • Cumulus-aided transfer technique.
  • Prednisolone.
  • Local injury.
  • Traditional chinese herbal remedy.
  • Piroxicam.


Newer modalities of treatment

  • Many therapeutic options to treat the endometrial dysfunction and thereby improve pregnancy rates have been tested. Endometrial gene therapy, local endometrial stimulation could be introduced in the future into the routing clinical setting.
  • A genomic tool named the endometrial receptivity array, based on a customized microarray, containing 238 genes.
  • This tool has proven to be more accurate and consistent at identifying the personalized window of implantation (WOI) day.


Conclusion

  • Endometrium exhibits a short period of receptivity known as the WOI approximately 6 days after ovulation for 4-5 days.
  • Embryo implantation and clinical on going pregnancy rates are significantly higher in patients with endometrial thickness of 9-10 mm.
  • Improvement in the uterine vascularity could improve pregnancy rates in a patient with a thin endometrium. Low-dose aspirin, low-molecular-weight heparin, vaginal sildenafil, pentoxifyline, tocopherol ang L-arginine are some agents which may use to improve implantation.
  • Pathological conditions such as fibroids, intra-uterine adhesions, endometriosis, uterine spectrum, hydrosalpinx, endometrial polyps, endometriosis, adenomyosis, polycystic ovary syndrome and auto-immune conditions should be addressed first prior to assisted reproductive technologies.


Role of IVIg, intralipid, allogeneic lymphocyte therapy, acupuncture, local injury, traditional Chinese herbal remedy and nonsteroidal antiinflammatory drug look promising but further studies are required to establish their efficacy.


  Ultraviolet air purification system for healthcare industry Top


Sudeep Sethi

SPC Heat Pipes FZC, Dubai, U.A.E, E-mail: sudeep.sethi@spcoils.ae

Healthcare buildings are built tight and insulted to combat energy loss and as a result of that biological and chemical concentrations continually rise within the building's envelope. HealthCare facilities face a myriad of indoor air quality (IAQ) issues from not bringing in enough outside air, not sterilizing the air, and that leads to bacteria thriving in such environment and multiply exponentially. Ultraviolet (UV) Air purification systems improve IAQ significantly and especially in the healthcare industry. UV air purifiers will neutralize biological contaminants such as mold, bacteria, viruses, spores, allergens, all kind of odors, and thousands of other airborne contaminants. UV energy disrupts the deoxyribonucleic acid of a wide range of microorganisms, rendering them harmless and eventually eradicating them from air. UV germicidal lamps are low pressure mercury lamps that emit UV energy at 254 nm and when applied in ducts for some time it purifies the air and keeps the system germ free and at the same time keeps the equipment more energy efficient and reduces replacement costs.


  Role of gnrh agonists as ovulation trigger Top


Shashi Singh

Dr. Singh's Test Tube Baby Centre, Meerut, India,

E-mail: drsashee@yahoo.in

Ovarian hyperstimulation syndrome (OHSS) is the price we pay for our attempt to override nature's delicate balances that were created to assure single oocyte ovulation. Spontaneous OHSS does occur; however, it is very rare. Human chorionic gonadotropin (hCG) is used as a surrogate to luteinizing hormone (LH) for the purpose of oocyte maturation and induction of ovulation. Given its significantly longer half-life (>24 h vs. 60 min for LH1, 2), hCG administration results in a prolonged luteotrophic effect, characterized by the development of multiple corpora lutea, and supraphysiological levels of estradiol (E2) and progesterone (P). This sustained luteotrophic effect may result in the development of OHSS, still the most frequent and severe complication of ovarian stimulation treatments, a complication that can be totally prevented. The midcycle spontaneous LH surge is characterized by three phases: A rapidly ascending limb of 14 h duration, a plateau of 14 h, and a descending phase of 20 h. The parallel follicle-stimulating hormone (FSH) surge is of lower amplitude. Serum E2 levels reach a peak at the time of the onset of LH surge and then decline rapidly. Serum levels of P begin to rise 12 h before the LH surge, continue to rise for an additional 12 h, and then plateau until follicular rupture (36 h after LH surge onset). Follicular rupture is associated with a second rise in P and a fall in E2 as a luteal pattern of ovarian steroidogenesis Gonadotropin-releasing hormone agonist (GnRHa) elicits pituitary secretion of gonadotropins, which can be used for triggering oocyte maturation and ovulation, if given at the right time of the cycle. HCG is used as a surrogate to LH for the purpose of oocyte maturation and induction of ovulation. Given its significantly longer half-life (>24 h vs. 60 min for LH, hCG administration results in a prolonged luteotrophic effect, characterized by the development of multiple corpora lutea, and supraphysiological levels of E2 and P. This sustained luteotrophic effect may result in the development of OHSS, still the most frequent and severe complication of ovarian stimulation treatments, a complication that can be totally prevented GnRHa elicits pituitary secretion of gonadotropins, which can be used for triggering oocyte maturation and ovulation, if given at the right time of the cycle. The injection of GnRHa results in an acute release of LH and FSH. Serum LH and FSH levels rise for 4 and 12 h, respectively, and are elevated for 24-36 h. The amplitude of the surge is similar to that seen in the normal menstrual cycle, The most important benefit emerging from the use of GnRHa rather than hCG for ovulation induction is the ability of this regimen to completely eliminate the threat of clinically significant OHSS.


  Elonva in poor responders Top


Shahar Kol

IVF unit, Rambam Health Care Campus, Israel Institute of Technology, Haifa, Israel, E-mail: skol@rambam.health.gov.il

Poor ovarian response (POR), as defined by the Bologna Criteria in 2011, remains a significant challenge in the field of assisted reproductive technologies (ART). Numerous protocols and interventions have been introduced in the treatment of POR, however, there is insufficient evidence to support the routine use of any particular intervention or protocol either for pituitary down-regulation, ovarian stimulation, or adjuvant therapy in the management POR in in vitro fertilization (Cochrane Library 2010). Elonva (corifollitropinalfa), has specific pharmacodynamics and kinetics which significantly differ from all available gonadotropin preparations. Therefore, it offers a new opportunity in the treatment of POR. The available literature so far is of a retrospective nature, so firm conclusions cannot be drawn. However, data so far hint for a possible advantage of using Elonva in POR <40 years of age. A randomized controlled study is underway and will probably give us more firm conclusions.

There are 3 potential advantages for using Elonva in POR:

  • Very sharp early follicular phase rise in blood follicle-stimulating hormone (FSH) which may act to recruit the maximal available follicles.
  • A decreasing FSH levels during the follicular phase, after a sharp peak is attained, which resembles FSH levels dynamics in the natural cycle, and may contribute to better oocyte quality.
  • The psychological effect of using less injections and easier treatment burden among POR who are prone to have repeated in vitro fertilization cycles.


In conclusion, Elonva is an important addition to our fertility drugs arsenal, the advantage of which in the treatment of POR is yet to be defined by randomized controlled studies and by personal experience by each treating physician in the field of ART.


  Human Chorionic Gonadotropin For Trigger - Recombinant Or Urinary? Top


Sandeep Karunakaran

ART Centre, Army Hospital, New Delhi, India,

E-mail: sandeep_kk@yahoo.com

The preovulatory surge of luteinizing hormone (LH) provides the physiologic stimulus for final oocyte maturation and induces ovulation, during which the ovarian follicle releases the mature oocyte that is picked up by the infundibular fimbria of the oviduct. It is well-known that human chorionic gonadotropin (hCG) and LH have similar molecular structure and share 80% homology. Their capacity for binding to the same receptor was demonstrated more than 20 years ago. In assisted conception, urinary (u) hCG has been used for several years to mimic the endogenous LH surge as there are considerable structural similarities between hCG and human (h) LH, and hence, both hormones stimulate the same receptor. hCG is readily available in the urine of pregnant women, whereas only low concentrations of LH are found in the urine of postmenopausal women. Urinary preparations, however, are associated with a number of disadvantages, including an uncontrolled source, lack of purity, and batch-to-batch variation in activity leading to variable clinical results. Recombinant hCG (rhCG) was recently introduced as an alternative to urinary hCG for the final maturation of oocytes in women treated with IVF and ICSI. rhCG is derived from genetically engineered Chinese hamster ovary cells through recombinant deoxyribonucleic acid technology. This product has a high purity that facilitates characterization and quantitation by phsycochemical means, reducing the need for animal bioassays. Over the years, many studies have been formulated and completed to compare the two types of hCG. The initial studies were in favor of the urinary products. Later, the studies found that rhCG, 250 µg, and uhCG, 5000 or 10000 IU are equally effective in inducing follicular maturation in women undergoing assisted reproductive technologies. Nowadays, the studies increasing point in favor of recombinant products. The talk will focus on how to get the best of both the worlds. It would focus on understanding the strengths and weaknesses of these products and utilize them to benefit the infertile patients to become parents.


  Monitoring of endometriu Top


Sam P Abraham

Abraham's Infertility Centre, Changanacherry, India,

E-mail: drsampabraham@hotmail.com

On 2D ultrasound an endometrium of 6 mm or more in thickness, preferably 8-10 mm that is multilayered is good enough. However, its morphological assessment is essential. Because of orderly organization of glandular elements in proliferative phase, endometrium is generally hypoechoic in this phase, though the morphology can be graded. Grade A Endometrium: Multilayered with intervening area more echogenic than myometrium. Grade B Endometrium: Multilayered with intervening area hypoechoic to myometrium. Grade C Endometrium: Homogenous hyperechoic endometrium. B mode ultrasound assesses the anatomy of the endometrium but its functional maturity can be assessed by Doppler of spiral arteries. Spiral arteries supply the endometrium and these are the vessels that undergo substantial changes during menstrual cycle. estrogen causes vasodilatation and progesterone antagonizes the effect. Therefore higher E2/P ratio is responsible for higher blood flow through uterine vascular bed. Thus endometrial color Doppler gives direct information about estrogen and progesterone levels and in turn also about functional maturity of the follicle and endometrium. On color Doppler, the vascularity of the endometrium is classified by Applebaum Zone I: Blood vessels reaching myometrium surrounding the endometrium Zone II: Blood vessels reaching hyperechoic endometrial edge. Zone III: Blood vessels reaching internal endometrial hypo echoic zone Zone IV: Blood vessels reaching endometrial cavity. On pulse Doppler, these blood vessels should show resistance index (RI) 0.49-0.59 and pulsality index (PI) 1.1-2.3. This vascularity should cover 5 mm area of a particular (3-4) zone of endometrium. Even if transvaginal color Doppler (TVCD) of follicle is normal, endometrial and the uterine artery indices should be within normal limits for implantation. Therefore even with mature follicle if endometrial vascular parameters are not achieved, stimulation is to be continued apart from endometrium and follicle it is also essential to evaluate the uterine artery flow on the dominant side before human chorionic gonadotropin. estrogen receptors are present in uterine arteries and cause vasodilatation in these vessels also. The normal values of uterine artery indices are RI 0.60-0.80 and PI 2.22-3.16. Even if TVCD of follicle is normal, endometrial and the uterine artery indices should be within normal limit for implantation.


  Oocyte Cryopreservation: Time To Chill Top


Rashmi Goenka, Deepak Goenka

Institute of Human Reproduction, Guwahati, India,

E-mail: rashgoenka@yahoo.com

During the past three decades, the industrialized world has witnessed an increase in the age at first birth and the number of women delaying childbearing. Further adding to this burden is the fact that pregnancies conceived at an advanced maternal age are more often associated with aneuploidy and spontaneous abortion. Advancements in cancer therapies have also led to dramatic improvements in long-term survival. In view of the reproductive risks of cancer therapies, there has been growing interest in expanding the reproductive options for cancer patients. These have led to the evolution in reproductive technologies and most notably oocyte cryopreservation. Although it has been more than 25 years since the first birth from oocyte cryopreservation has been reported, due to technical difficulties specific to the oocyte, it was until early 2000s, when larger series of success began to appear. In the past few years, there is good evidence that fertilization and pregnancy rates from cryopreserved oocytes are similar to those of fresh oocytes and safety evidence suggests that it does not pose added risk in chromosomal abnormalities, birth defects or developmental deficits. In view of this success, American society for reproductive medicine on 22, October 2012, has made a decision to remove the technology's experimental designation for medical indications. Oocyte cryopreservation is now being offered to reproductive age women diagnosed with malignancy and became a viable option prior to gonadotoxic therapy for postpubertal girls, single women, and those who have moral/ethical objections to freeze embryos. It is now available to women seeking fertility preservation for nonmedical indications too. It is also indicated when there is difficulty of sperm collection, inadequate seminal samples, nonviable spermatozoa, or unavailability of partner at the time of oocyte retrieval. Finally, egg donor programs have become more simplified and efficient. The oocytes can be quarantined, enabling the donors to be screened for transmissible disease. Furthermore, the donors and recipients are not required to synchronize their menstrual cycles. Recent studies reveal that vitrification is a very efficient method for oocyte cryopreservation. This has been attributed to the elimination of mechanical injury caused by intracellular and extracellular ice crystal formation. Studies have reported improved survival, pregnancy rates, and faster-meiotic spindle recovery in vitrified oocytes. Oocyte cryopreservation popularity appears to be gaining, and it is anticipated that there will be a significant increase in the number of women seeking oocyte cryopreservation services in the coming years as this technology continues to improve and offer great potential.


  Understanding downregulation Top


Ramadevi Papolu

Dr. Rama's Institute for Fertility, Hyderabad, India,

E-mail: ramafertility@yahoo.com

Introduction: Ovarian stimulation is an important key for the success of in vitro fertilization and embryo transfer (IVF-ET) treatment. Several protocols are available for IVF-ET. The review summarizes the main differences and the clinical characteristics of the protocols in use with gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. Objective: The combination of exogenous Gonadotropin plus a GnRH agonist, which is able to suppress pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. But the synchronous follicular development, pregnancy rates are compromised. GnRH-a long protocol, induces profound suppression of endogenous release of gonadotropins during the early follicular phase, allowing the early antral follicles to grow coordinately in response to exogenous gonadotropins to accomplish simultaneous maturation. This leads to an extended widening of the FSH window, an increased number of recruited mature follicles and a higher number of retrieved oocytes. The use of GnRH agonists in the long protocol is characterized by some disadvantages also namely long treatment period until desensitization occurs, increased risk of ovarian hyperstimulation syndrome and some side effects. Conclusion: Randomized clinical trials, retrospective, as well as prospective analysis in our experience, demonstrate that GnRH long protocol is associated with higher pregnancy rates and live births as compared to the use of gonadotropins without GnRH-a. The major benefits of these drugs include decreased cancellation rate through prevention of premature LH surge and luteinization, enhancement of follicular recruitment, allowing the recovery of a larger number of oocytes, and the improvement in routine patient treatment schedule which is the rationale for successful IVF-ET treatment.


  Time lapse monitoring Top


Peter Kovacs

Kaali Institute, IVF Center, Budapest, Hungary,

E-mail: peterkovacs1970@hotmail.com

One of the "complications" of in vitro fertilization (IVF) that still needs to be addressed is the relatively high rate of multiple pregnancies. The solution seems to be easy; one has to transfer a single embryo. Most IVF centers use selection based on morphology to identify the embryo(s) for transfer. This method is associated with suboptimal efficacy as on average 20-40% of embryos identified will implant resulting in about 30-35% pregnancy rate. During the last 10-15 years, various methods to improve embryo selection have been tested. One of these methods is time-lapse technology. Incubators equipped with time lapse units enable the embryologist to observe the embryo continuously without removing it from the optimal culturing conditions. Significantly, more information can be collected about the kinetics of cleavages, morphologic changes, and the dynamics of blastocyst development this way. The safety of the technology has been confirmed by several studies in which embryos obtained from sibling oocytes were randomly cultured in time lapse units or under standard conditions. Embryo development, blastocyst formation, and pregnancy rates have not differed. Several retrospective studies correlated morphokinetic events with day 3 embryo development, blastocyst formation, and implantation potential. These studies have found that when the duration of the 1 st , 2 nd , 3 rd mitosis, 1 st , 2 nd cytokinesis and the time to the 5-cell stage fall within an optimal range there is a higher likelihood for the embryo to turn into blastocyst and to implant. It was also found that embryos that cleave directly from 1 to 3 cells, have uneven blastomeres at the 2-cell stage and are multinucleated at the 4-cell stage have minimal chance to implant. Furthermore, both early cleavage kinetic markers and the time required to reach the blastocyst stage correlated with euploid status. There is, however, relatively little information available about the impact of time-lapse monitoring on pregnancy rates. In addition, data regarding obstetric outcome need to be collected. Prospective studies should evaluate how those models for embryo selection developed based on kinetic markers perform compared with standard morphologic screening. Finally, it should be tested how time-lapse monitoring could be combined with other embryo screening tools to optimize embryo selection during IVF.


  Mild ovarian stimulation using anastrozole/human menopausal gonadotropin (hmg) and tamoxifen/hmg for in vitro fertilization-our results Top


Neela Baheti

Baheti Hospital and Centre for Reproductive Health Care, Jaipur, E-mail: nvbaheti@gmail.com

Objective: To evaluate the efficacy of mild ovarian stimulation in terms of clinical pregnancy rates, miscarriage rates, multiple pregnancy, and congenital anomalies. Study Design: Retrospective Study. Setting: Private practice. Materials and Methods: 305 patients had 412 cycles of in vitro fertilisation/intracytoplasmic sperm injection from January 2011 till May 2014. Their age ranged from 24 to 43 years. There were 157 cycles of gonadotropin-releasing hormone agonist down-regulation and 134 cycles of conventional antagonist protocol. Mild stimulation was given using anastrozole/human menopausal gonadotropin (HMG) and tamoxifen/HMG to 40 and 25 patients, respectively. anastrozole/HMG was given to patients with previous history of ovarian hyperstimulation syndrome with conventional agonist protocol. Tamoxifen/HMG was given to patients with previous poor response, potential poor responders, and patients with financial restraint. Results: Overall clinical pregnancy rate was 24.20% in conventional down-regulated cycles, 32.83% in antagonist cycle, 32.5% in anstrozole/HMG cycles, and 20% in tamoxifen/HMG cycles. Miscarriage rate was the highest -28% in agonist cycles versus 22% in antagonist cycles versus 20% in mild stimulation group. Multiple pregnancy rate was 20% in antagonist group versus 18% in down-regulation versus 25% in anastrozole/HMG group and 6.9% in the tamoxifen group. There were no congenital anomalies in any of the groups studied. Use of tamoxifen and anastrazole significantly reduces the dose of gonadotropins. Tamoxifen further reduces the cost of stimulation due to its continuous use till the day of human chorionic gonadotropin trigger prevents premature luteinizing hormone surge, thus, obviating the use of the antagonist. None of the patients in the tamoxifen group had premature ovulation. Conclusion: Mild stimulation gives good pregnancy rates, low miscarriage rate, less morbidity, fewer cancelations, and reduced economic burden.


  Arcuate Uterus And Pregnancy Loss: WhİCh Is The Cause And Which Is The Outcome? Top


Mete Isikoglu

GELECEK the Center for Human Reproduction, Antalya, Turkey, E-mail: misikoglu@gmail.com

Which came first: The hen or the egg? The similar paradox in the relation of the arcuate uterus and the pregnancy loss continues confusing the minds and the practices of in vitro fertilization (IVF) specialists. This paradox results in the dilemma of performing a hysteroscopic correction or not. We claim that the etiopathogenesis of septate and subseptate uteri may be completely different from that of arcuate uteri. Septate and subseptate uteri are absolutely congenital while the latter may be acquired that is, experiencing a pregnancy increases the thickness of the fundal myometrium whatever regardless of the outcome of the gestation. This hypothesis is supported by the findings in the present study which shows that fundal myometrial thickness is thicker in women with a history of healthy deliveries compared with those of women diagnosed with unexplained primary infertility and those with a history of pregnancy loss. Furthermore, within the group of patients with pregnancy loss, there was a tendency toward a thicker Fm as the number of abortions increase, but it did not reach a statistically significant level. The proposals of the existing studies claiming a relation between an arcuate uterus and pregnancy loss are based on two main findings:

  • Higher prevalence of arcuate uteri in recurrent miscarriage cases.
  • Similar pregnancy loss rates compared with those of normal uteri after correction of arcuate uteri.


The first proposal can simply be opposed by the theory that pregnancy itself (even if it is lossed) is the cause of myometrial hypertrophy resulting in the arcuate structure. For the second proposal, there can be two objections: (a) Even diagnostic hysteroscopy with completely normal findings prior to IVF has been shown to increase pregnancy rates (b) Performing hysteroscopy itself may have a beneficial effect by various ways especially immunomodulation or via local mediators. It is possible that irrigation of the uterine cavity with saline at the time of a recent hysteroscopy may have a beneficial effect on implantation. Taking into consideration, the lack of a clear quantification and the inconsistency of the criteria used to define an arcuate uterus make our proposal stronger. While waiting for the results of future randomized controlled trials, treatment decisions should be very limited to only for symptomatic patients with high suspicion and without otherwise identifiable etiology.


  Mild Ovarian Stimulation: When And How? Top


Khaled Terras

Center for Reproductive Medicine and Prenatal Diagnosis, Clinique Internationale Hannibal, E-mail: khaledterras@voila.fr

Ovarian stimulation to achieve multiple follicle development has been an integral part of in vitro fertilization (IVF) treatment. In the context of improved laboratory performance, the need for a large number of oocytes as an integral part of a successful IVF program may be questioned. The aim of this lecture is to summarize the studies performed during the last decade to develop the concept of mild stimulation aiming to obtain fewer than eight oocytes. Here, we examine the balance between IVF success and patient discomfort, and complications and cost, and how these might improve by simpler ovarian stimulation protocols aimed at retrieving fewer oocytes. We intend to analyze why progress has been rather slow and why there is much resistance to mild stimulation.

The strength of mild stimulation protocols may be:

  • Similar live birth rates/started treatment.
  • Reduced complexity, patient discomfort, and risk.
  • Reduced cost.
  • Beneficial effect on oocyte/embryo quality.


The weakness may be:

  • Lower pregnancy rates per cycle.
  • Less margin for suboptimal laboratory performance.
  • Fewer embryos for cryopreservation.
  • Lack of "robustness".


Based on the evaluation of the results of using mild stimulation protocols, we try to rethink the definition of "successful" better representing the interests of the woman, the child, and society.


  Ovarian Drilling: Indications And Results Top


Issam Lebbi

Department of Obstetrics and Gynecology, Fertility Private Clinic, Dream Center, Tunisia, E-mail: issam.lebbi@planet.tn

Polycystic ovary syndrome (PCOS) is a common disorder, affecting approximately 5-10% of infertile women. It is the cause of over 70% of cases of infertility due to anovulation. The main goal of treatment is the induction of mono-ovulatory cycles. Weight loss and clomifene citrate (CC) are the first-line components of patient's treatment before gonadotropins use. However, during gonadotropin administration, there is a high risk of ovarian hyperstimulation syndrome and multiple pregnancies. Surgical therapy with laparoscopic ovarian drilling (LOD) is often used before gonadotropins in order to obtain normal ovulatory cycles. The most plausible mechanism of action, if LOD is the destruction of ovarian follicles and a part of the ovarian stroma, inducing a reduction of serum androgens and inhibin levels which results in an increase of FSH and recovery of the ovulation function. LOD may also increase ovarian blood flow, allowing a high delivery of gonadotropins and postsurgical local growth factors. An improvement of insulin sensitivity after LOD has also been suggested. The common technique of LOD is the use of monopolar electrocautery (diathermy) or laser, with comparable results. Normally, three to eight diathermy punctures are performed in each ovary, leading to further normal ovulation at 74% of the cases into 3-6 months period. More than eight punctures seams to increase the occurrence of postoperative pelvic adhesions and decrease the ovarian reserve. Different other minimally invasive techniques were later described for ovarian drilling. A systematic Cochrane review concluded that there was no evidence of a significant difference in rates of clinical pregnancy, live birth, or miscarriage in clomiphene-resistant PCOS women undergoing LOD compared to other medical treatments. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive.

A comprehensive review of ovarian drilling for PCOS concluded that ovarian drilling leads to spontaneous restoration of fertility in 20-64% of women with PCOS who had previously been infertile as a result of anovulation and who did not respond to clomiphene citrate treatment. Several factors could influence the efficacy of ovarian drilling: A higher likelihood of success in patients with elevated luteinizing hormone concentrations (>10 IU/l) and <3 years of infertility. However, other factors such as body mass index, insulin resistance, and testosterone concentrations are contradictory. All meta-analysis confirmed that LOD is a second-line treatment in PCOS patients, especially those with CC-resistance. The main benefits are shorter time to pregnancy and less need to ovulation induction drugs. The other advantages of this technique are more comfort, cost-effectiveness, and performed ambulatory. However, LOD is not superior to CC as a first-line of ovulation induction treatment in women with PCOS.


  Recombinant luteinizing hormone in poor responders Top


Devika Gunasheela

Gunasheela Surgical and Maternity Hospital, Bangalore, India, E-mail: gunasheelaivf@gmail.com

Luteinizing Hormone (LH) and follicle stimulating hormone are the two key hormones that work in synergy while stimulating follicular growth and ovulation. However, the role of LH in stimulation of follicular development, optimal dosages, its importance in older patients and patients with poor ovarian reserve, has been a topic of discussion.

It is now clear that there are three categories of patients who would require supplementation of LH during stimulation protocol, and these would be mainly the:

  • Hypogonadotropic hypogonadism.
  • Normogonadotropic poor response.
  • Patients with advanced age and poor ovarian reserve.


The Asia pacific fertility advisory group (2011), defined suboptimal ovarian response as:

  • Having no follicle >10 mm by day 6 (De Placido et al., 2005).
  • Low estradiol concentration <200 pg/ml by day 6 (Vuong et al., 2004).
  • poor progression or slowing of follicle growth, that is, previously 1-2 mm progression/day slowing to <2 mm in 3 days.


Gunasheela IVF centre Statistics

Study Period-January-December 2012


The initial study showed that:

  • 27 patients identified retrospectively who were poor responders and in whom recombinant luteinizing hormone was used for ovarian stimulation.







  Scheduling Gonadotropin-Releasing Hormone Antagonist Cycles Top


Baris Ata

Department of Obstetrics and Gynaecology, Uludag University of Bursa, Turkey, E-mail: barisata@hotmail.com

Gonadotropin-releasing hormone (GnRH) is a decapeptide released at the hypothalamic level which stimulates the pituitary secretion of both luteinizing hormone (LH) and follicle-stimulating hormone and thus, controls the hormonal and reproductive function of the gonads. Blockade of GnRH effects may be needed to prevent premature LH surge during ovarian stimulation. Multiple amino acid substitutions in the GnRH structure yield GnRH antagonists that bind to the GnRH receptor and provide competitive inhibition of the naturally occurring GnRH. The fact that GnRH antagonists cause an immediate suppression of gonadotropin concentrations while preserving pituitary responsiveness to endogenous GnRH provides flexibility in treatment. Prompt suppression of pituitary gonadotropins avoids the initial stimulatory phase of the agonists. Discontinuation of GnRH antagonist treatment leads to a rapid and predictable recovery of the pituitary-gonadal axis. So far, no systemic side effects and no major local reactions have been reported following the use of third-generation antagonists. The efficacy of these agents in preventing premature LH surge has been demonstrated by several studies. Currently, two treatment protocols of GnRH antagonists are used in clinical practice: The multiple-dose protocol and the single-dose protocol. Both protocols are effective and well-tolerated. Currently, luteal phase hormonal supplementation is commonly administered in assisted reproductive technologies (ART) cycles. The rationale for luteal phase supplementation in ART derives from concerns that the act of follicular aspiration may disrupt sufficient volume of granulosa cells to impair the luteal steroidogenesis and from evidence that the incidence of the luteal inadequacy is increased in patients who underwent superovulation. There are conflicting results about the benefit of luteal phase supplementation. In general, the antagonists appear to be associated with a lower risk of ovarian hyperstimulation syndrome than do agonists. Using a GnRH agonist instead of human chorionic gonadotropin for triggering ovulation in antagonist used cycles will possibly reduce the risk further. It seems that the competition between antagonists and agonists will not come to an end in the near future and GnRH antagonists have the chance of replacing agonists in ovarian stimulation treatment for assisted reproduction techniques.


  Corifollitropin, A Clinician's Perspective Top


Baris Ata

Department of Obstetrics and Gynaecology, Turkey,

E-mail: barisata@hotmail.com

Corifollitropin is a designer's molecule generated by adding the carboxyterminal peptide of the human chorionic gonadotropin molecule to follicle-stimulating hormone (FSH) molecule. This modification increased half-life of FSH to 96 h, allowing continuous stimulation for a couple of days. The advent of corifollitropin is absolutely exciting. It has been rigorously tested in a series of clinical trials including the European network for genetic and genomic epidemiology trial, which is the largest randomized controlled trial in the field of infertility until today. These trials convincingly show that this new molecule is not immunogenic, is an effective substitute for daily FSH injections during the first few days of controlled ovarian stimulation in normoresponders, and does not seem to be associated with congenital anomalies in the assisted reproductive technologies offsprings. On the other side of the coin, the suggested dosing scheme for lean patients seems questionable, as there was a clinically significant difference between live birth rates in favor of daily FSH injections in the ENSURE trial. Data on poor responders and hyper-responders are very limited or missing. Unfortunately, the price gap between average stimulation cycle with corifollitropin and daily recombinant follicle stimulating hormone is relatively high. What is the value placed on cutting down number of injections needs to be discussed with patients.


  Pragmatic approach to successful (in vitro maturation, in vitro fertilization and embryo transfer) Top


Aisaku Fukuda

Department of Reproductive Endocrinology and Infertility, IVF Osaka Clinic, 1-1-14 Nagata-higashi Higashiosaka, Osaka, Japan, E-mail: fukuda@ivfosaka.com

In vitro maturation, in vitro fertilization (IVM-IVF) is a relatively new option for assisted reproductive technologies (ART) promising significant benefits such as prevention of ovarian hyperstimulation syndrome (OHSS), lower cost, and less stress. However, IVM-IVF success rates are thought to be less than conventional ART. We have been using IVM-IVF as a routine ART choice mainly for polycystic ovary (PCO) patients for last 11 years. In the meantime, IVM-IVF was performed in 609 cycles of PCO (355 cycles) and regular cycling patients (254 cycles). Follicular monitoring began from day 7, and 150 units/day of follicle-stimulating hormone were administered for 3 days on average for some patients until follicles reached 8 mm in diameter. Human chorionic gonadotrophin was administered 36 h before oocyte retrieval. Immature oocytes were cultured in IVM medium (Oligio) supplemented with 10% SSS (Irvine) for 26 h, and intracytoplasmic sperm injection was performed on matured oocytes. Day-3 embryos or blastocyst were transferred (Fresh group). However, fertilized oocytes were vitrified and transferred in a subsequent cycle when endometrium stripe was <8 mm (Frozen group). Clinical outcome was evaluated. There was no significant difference in demographics of the patient between the two groups. The clinical pregnancy rates of the fresh group, frozen group, and total were 30%, 22%, and 28%, respectively. Pregnancy rate of the fresh group (30%) was significantly higher than frozen group (22%, P < 0.01). Total number of babies born were 84 (61 from fresh cycles and 23 from frozen cycles), and no malformation was found. The percentage of PCO patient in general was 58%. However, significantly more PCO patients were included in the fresh group (69%) than in frozen group (43%, P < 0.01). Our data suggest that IVM-IVF is acceptable treatment choice of ART from the point of clinical outcomes and risks of OHSS. Fresh method is better for PCO patients, and frozen method is better for regular cycle patients. Moreover, IVM-IVF seems to be a safe treatment from the babies born by IVM-IVF. IVM-IVF should be considered as a routine choice of ART, especially in PCO patients.

9 th August 2014


  Evidence Based Management of Poor Responders In Assisted Reproduction Top


Hassan N Sallam

Department of IVF, University of Alexandria, Alexandria Fertility, Center, Egypt, E-mail: nooman.sallam@hotmail.com

It is estimated that about 10% of women treated with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are "poor responders", but various criteria have been used to define this condition (Surrey and Schoolcraft, 2000). In order to establish an objective definition, we have constructed receiver operating characteristic curves for our patients and found that, based on our results, poor responders are patients from whom <5, 6 or 8 oocytes are retrieved, when undergoing treatment with ICSI, IVF or testicular sperm extraction/ICSI, respectively (Sallam et al., 2005). A new definition has also been proposed by the ESHRE Bologna group but has been widely criticized as non evidence-based (Ferraretti et al., 2011).Various regimens have been suggested and used for the treatment of poor responders. These include increasing the dose of human menopausal gonadotropins (HMG), using purified HMG or recombinant follicle-stimulating hormone (recFSH), starting FSH stimulation in the late luteal phase, diminishing the duration of gonadotrophinreleasing hormone agonist (GnRHa) (flareup protocols), diminishing the dose of GnRHa, using GnRH antagonist (single or multiple dose protocols), performing IVF/ICSI in natural unstimulated cycles (with or without GnRH antagonists), adding clomiphene citrate, growth hormone, testosterone, dehydroepiandrosterone or L-arginine to HMG/FSH stimulation. Randomized trials have shown that the addition of GH (Duffy et al., 2010) or testosterone gel (Kim et al., 2011) increase the clinical pregnancy rate significantly. In addition, in one small randomized controlled trial, the use of recFSH may also be of benefit (Raga et al., 1999).


  Is there a role for dehydroepiandrosterone supplementation in women with diminished ovarian reserve? Top


Kunjimoideen Kinattingal

ARMC IVF Fertility Centre, Kozhikode, India.

E-mail: drkmoideen@gmail.com

Dehydroepiandrosterone (DHEA) supplementation for poor responders may improve ovarian response and in vitro fertilization (IVF) treatment outcome. The mechanism of action of DHEA, and specifically, the stage of folliculogenesis influenced by DHEA are studied. In a prospective, self-controlled study of poor responders to IVF treatment, comparing day 3 biochemical (antiMullerian hormone [AMH], inhibin B and follicle-stimulating hormone [FSH]) and ultrasound (antral folliclecount [AFC]) ovarian reserve markers and IVF treatment outcome before and after DHEA supplementation of at least 3 months duration were reviewed. Following DHEA, there was a significant increase in AFC (P = 0.0003) without significant changes in the baseline biochemical parameters AMH, inhibin B, or FSH. The enhanced response comprised increased peak estradiol levels (P = 0.0005), number of follicles and gt; 15 mm, oocytes, metaphase II oocytes and embryos (P = 0.004, P = 0.00001, P = 0.0004 and P = 0.0006, respectively) and oocytes number/total FSH dose (P = 0.0009). The proportion of cancelled cycles due to very poor response decreased significantly (P = 0.02). DHEA does not appear to exert influence via recruitment of preantral or very small antral follicles (no change in AMH and inhibin B) but rather by rescue from atresia of small antral follicles (increased AFC).


  Vitrification: The Only 100% Success Story In Assisted Reproductive Technologies Luis Arturo Ruvalcaba CastellΣN Top


Luis Arturo Ruvalcaba

Department of Obstetrics and Gynaecology, Medical Center Specialty Hospital Puerta de Hierro, Guadalajara,

E-mail: drlarc@hotmail.com

The vitrification is an ultra-rapid cooling technique that offers a new perspective in attempts to develop an optimal cryopreservation procedure for human oocytes and embryos. This type of cryopreservation, has progressed to become a useful tool in human in vitro fertilization to cryopreservate human oocytes, embryos, and blastocysts. There are several unique biological characteristics of human oocytes that might be susceptible to damage during the cryopreservation procedure such as the meiotic spindle, the cytoeskeletal elements and the cortical granules. The exposure time to the cryoprotectant solutions, the concentration of the cryoprotectant, as well as an extra and intracellular ice formation are critical factors affecting the viability of the oocyte. The vitrification method produces a glass-like solidification of cells, avoiding intracellular ice crystallization during the cooling and warming process. This method was described by Masashigue-Kuwayama in 2005, using cryoprotectants with higher membrane permeability and lower toxicity that diminishes the cytotoxicity of the cryoprotectants used in the past. This type of techniques are not expensive and can be obtained by one embryologist within a few minutes. All these characteristics that includes less damage to the cells by the cryoprotectors, the existence of permeating and nonpermeating cryoprotectors to reduce the possibility of cell damage during the process, the less time required compared to other methods like slow freezing, the lower temperature rates achieved during the process (exposition to -23,000 C/min and -196 C in storage), and a high survival rates of the oocytes, embryos or blastocyst, are some of the characteristics that permits this cryopreservation method to be the only 100% success story in ART. Vitrification is an alternative method of cryopreservation in artificial reproductive techniques, resulting in significantly improved survival rates of oocytes and embryos, and with excellent clinical outcomes. To reduce the risk of viral contamination, is stipulated that nonserum substitutes must be used. Synthetic macromolecule, hydroxypropylcellulose, for use as a supplement in vitrification solutions, reporting survival rates of 100% after thawing process.


  Dopamine agonists prevent or reduce the severity of ovarian hyperstimulation syndrome in women undergoing assisted reproduction? Top


Neelam Ohri

Newlife Rotunda Advanced Fertility Center, Varanasi, Uttar Pradesh, India, E-mail: drneelamohri@gmail.com

Introduction: In recent times, the dopamine agonist (DA), cabergoline has been introduced as a secondary prevention intervention for ovarian hyperstimulation syndrome (OHSS). Vascular endothelial growth factor (VEGF), expressed in human ovaries, is the most important mediator of human chorionic gonadotropin (hCG) dependent ovarian angiogenesis. VEGF activates receptor-2 (VEGFR-2) which induces vascular changes, and this effect is prevented by receptor blockade do (Gomez et al.). Cabergoline partially inhibits the ovarian VEGFR-2 through a decrease in its phosphorylation levels (Endocrinology 2006). And it was observed that high VEGF expression and activity in OHSS is associated with reduced dopamine production. The rationale for using cabergoline: Cabergoline counteracts the increased production of VEGF by the follicles after hCG administration (Cochrane Database Syst Rev 2012). It has similar effects to antiangiogenic drugs on vascular permeability and appears not to exert undesirable side effects (Garcia-Velasco 2009). In a systematic review and meta-analysis, Youssef et al. concluded that prophylactic treatment with cabergoline reduces the incidence but not the severity of OHSS. A statistically significant reduction in OHSS was observed in the cabergoline treated group (Cochrane Review, 2012). The use of DAs appears to be effective for the prevention of OHSS but less effective for the treatment of OHSS (Systematic review and meta-analysis (Baumgarten et al.). According to a recent systematic review and meta-analysis cabergoline reduces the risk of moderate-severe OHSS (Fertility and Sterility, 2014). As far as the dose of cabergoline and time of initiation of treatment is concerned, there is clinical heterogeneity between trials. Effect on endometrial angiogenesis: No difference in clinical pregnancy rates and miscarriage rates between the groups was found which may mean that endometrial angiogenesis is not affected. No difference in the live birth rate was observed. There was no increased rate of congenital malformations. Safety: Short-term use of cabergoline for preventing OHSS represents no significant risk for women. Conclusion: Dopamine agonist as a secondary preventive treatment leads to a significantly lower OHSS incidence in high-risk patients, especially for early onset OHSS without compromising pregnancy outcomes. It is less effective for the treatment of OHSS as it does not reduces the severity of OHSS.


  Ovarian Hyper Stimulation Syndrome-Current Acceptable Prevention Strategies Top


Neena Malhotra

Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India, E-mail:malhotraneena@yahoo.com

Ovarian Hyper stimulation syndrome (OHSS) is an iatrogenic complication of ovulation induction or ovarian stimulation for assisted reproductive techniques (ART). In severe forms affects 1-3% of ART cycles and is a potentially life threatening complication. Prevention strategies for OHSS can be classified as primary and secondary. Primary prevention is initiated before stimulation and includes personalizing stimulation protocols to suit individuals identified at high risk of OHSS that is, high responders. Secondary prevention includes strategies, as withdrawal, delay, or modification in stimulation protocols during the course of the stimulation cycle. Primary and secondary prevention strategies include:

Primary prevention

  1. Identifying women at high risk of OHSS before start of stimulation. These include:
    1. Women with polycystic ovary syndrome (PCOS).
    2. History of OHSS in prior cycles.
    3. High responders on the initial assessment as in high S. antiMüllerian hormone (>4.0 ng/ml), antral follicle count (>20 in total) in the absence of PCOS features.
  2. Choosing protocols: Antagonist protocols are preferred as are associated with lower risk of OHSS. Besides reducing the incidence of hospital admission consequent to OHSS, antagonist protocol reduces the need for secondary interventions such as coasting, or cycle cancellation (1).
  3. Insulin sensitizers: Use of insulin sensitizers including Metformin reduces the incidence of OHSS during ovarian stimulation (2).
  4. In vitro maturation (IVM): This technique stands to lower OHSS in women with PCOS or those with past history of sever OHSS. However, this strategy is not picked up owing to lower live birth rates as compared to standard in vitro fertilization technique.


Secondary prevention

During the course of stimulation, patients can be identified at risk of developing OHSS by monitoring response with estradiol levels or follicular tracking. Strategies of secondary prevention include:

  1. Coasting: This involves withdrawing gonadotropins and withholding human chorionic gonadotropin (hCG) trigger until the estradiol levels decrease to a safe level (<3,500 pg/ml). This method has the great attraction of the cycle not being cancelled, fresh embryos still being transferred and no additional gonadotrophins or medications being used (3). Although coasting is a very effective method to reduce the incidence of severe OHSS, it does not abolish the syndrome completely, as 2.5% of hyper-responders, still present with the severe form of the syndrome. The duration of coasting can vary between 3 and 9 days until the estradiol levels fall, however longer duration of coasting are associated with lower pregnancy outcome.
  2. Alternative agents to triggering ovulation:
    1. Agonist trigger: In gonadotrophinreleasing hormone antagonist cycles the use of agonist to trigger oocyte maturation is a recent and recommended strategy to prevent OHSS. Data from randomized controlled trial comparing agonist with hCG trigger have suggested a reduced but not eliminated incidence of severe OHSS after agonist trigger. The problem after agonist trigger is luteal insufficiency consequent to it. Luteal phase can be rescued by low dose hCG in doses after oocyte recovery (4). Further supplementation with estrogens and progesterone for luteal support improve pregnancy rate by correcting the luteal insufficiency.
    2. Recombinant luteinizing hormone: This appears an effective option, but excess costs and commercial non-availability are limiting factors to substitute this for hCG.
  3. Albumin: while initial experience suggested benefit recent evidence from RCT does not support the use of intravenous albumin to prevent OHSS (5).
  4. Hydroxyethyl starch (HES): Intravenous use of HES at the time of ovum pick up and in the initial 24 h has been suggested to benefit in the prevention of OHSS (5).
  5. Cryopreservation of embryos: Freezing all embryos and avoiding fresh transfer is a plausible strategy to prevent OHSS as pregnancy worsens the development of OHSS. This strategy is even advocated after agonist trigger when >20 oocytes are recovered as despite agonist trigger the patient is still at a high risk of developing OHSS less than combined use of agonist with freeze all policy seems to near eliminate the risk of OHSS in women at a higher risk (6).
  6. Dopamine agonist: The use of cabergolin, a dopamine agonist has proved useful in preventing severe OHSS however does not completely eliminate it. Used in patients at high risk of developing OHSS it can be started on the day or even before oocyte retrieval (7).
  7. Cycle cancellation: This is one of the strategies advocated, but with currently available methods, availability of other options the need for cycle cancellation to avert OHSS is by far less in current times. Conclusion: While no single strategy can eliminate the development of OHSS, combination helps to prevent t. Identification of women at high risk, use of antagonist protocol, agonist trigger, use of low dose hCG and freeze all would prevent OHSS and improve reproductive outcome in these women.



  Impact of ovarian reserve testing on assisted reproductive technologies success rates Top


Sandeep Talwar

Department of IVF, Bournhall Clinic, Gurgaon, India,

E-mail: sonutalwar2001@yahoo.co.in

  • Role of ovarian reserve testing.
  • Test of ovarian reserve should guide us in prognosticating outcome in individual cases by:
    1. Predicting the chances of pregnancy and live birth with or without treatment and
    2. Selecting an optimal dose of ovarian stimulation where treatment using ovarian stimulation is planned.
  • Test of ovarian reserve could have a pivotal role in guiding management throughout the fertility workup and treatment.


Tests for ovarian reserve are:

  • Follicle-stimulating hormone (FSH).
  • FSH/luteinizing hormone ratio.
  • Serum estradiol (E 2 ).
  • Antral follicle count (AFC).
  • Ovarian volume.
  • Anti-Müllerian hormone (AMH).


A single parameter is of limited value in predicting ovarian response to gonadotrophin stimulation in IVF patients.

  • AFC has a significant association with a number of eggs collected and with the likelihood of clinical pregnancy.
  • Panel of markers such as age, AFC, basal FSH and AMH, E 2 and inhibin-B could be useful in predicting ovarian response and optimizing the gonadotrophin stimulation protocol.


Although basal FSH, E 2 and inhibin-B are being classically used to infer gonadal function, the search for a marker that better reflects the quantity and quality of primordial follicles, and therefore the functional ovarian reserve, has led to scientific emphasis on AMH.


  How to preserve fertility in young women exposed to chemotherapy? The role of gonadotrophinreleasing hormone agonistic in addition to cryopreservation of embrya, oocytes, or ovaries Top


Zeev Blumenfeld

Department of Obstetrics and Gynaecology, Rambam Medical Centre, Haifa, Israel, E-mail: bzeev@tx.technion.ac.il

The late effects of cancer treatment have gained worldwide interest among hematologists, reproductive endocrinologists, oncologists, and all health care providers, and the protection against iatrogenic infertility caused by chemotherapy assumes a high priority. A prospective randomized study has found that gonadotrophinreleasing hormone agonistic (GnRH-a) protected the ovary against cyclophosphamide-induced damage in rhesus monkeys by significantly decreasing the number of follicles lost during the chemotherapeutic insult. A long-term follow-up of 240 children, 15 years of age or younger, treated for Hodgkin lymphoma (HL) showed azoospermia in 83% of the boys, whereas only 13% of the girls suffered premature ovarian failure. Since ovarian function was preserved in most long-term survivors who were treated prepubertally for lymphoma, but only in about half of similarly treated adult patients, it was clinically logical and therefore tempting to create a temporary prepubertal milieu in women in the reproductive age before and during the chemotherapeutic insult. We have administered a monthly depot intramuscular injection of GnRH-a analogue to more than 250 young patients exposed to gonadotoxic chemotherapy for malignant or nonmalignant diseases, after informed consent, starting before chemotherapy for up to 6 months, in parallel and until the end of chemotherapeutic treatment. Less than 7% developed irreversible hypergonadotropic amenorrhea. The remaining patients (>93%) resumed cyclic ovarian function, and 55 patients spontaneously conceived 82 times, and were delivered of 65 healthy neonates. These patients were compared to a control group of over 130 patients of comparable age (15-40), who were similarly treated with chemotherapy without the GnRH-a adjuvant. Neither the age, nor the diagnoses, ratio between Hodgkin's disease or non-HL differed between the two groups. Similar doses of radiotherapy exposure and ratios of patients treated by radiotherapy in addition to chemotherapy were experienced by the two groups. Moreover, the cumulative doses of each chemotherapeutic agent and the mean or median radiotherapy exposure did not differ between the groups. The rates of cyclic ovarian function, pregnancies and deliveries was significantly higher in the GnRHa co-treatment group versus control group. Our and others' results support the effectiveness of GnRH-a administration also to patients receiving cyclophosphamide pulses for systemic lupus erythematous and other autoimmune diseases. Recently we have experienced the first worldwide reported case of spontaneous successful deliveries of three healthy neonates after two repeated bone marrow transplantations, concurrently treated with GnRH-a during the gonadotoxic chemotherapy. How can we possibly explain the beneficial effect of the GnRH-a for minimizing the gonadotoxic effect of chemotherapy, in particular that of alkylating agents? Several explanations may be put forward:

  1. The hypogonadotropic state generated by the GnRH-a simulates the prepubertal hormonal milieu. One can conceivably hypothesize that the alkylating agents may bring about an increased rate of destruction/apoptosis of the nonresting follicles, and subsequently a decrease in the secretion of sex steroids and inhibins produced by these follicles, at different stages of maturation and differentiation. The resultant decrease in sex-steroids (estrogen, progesterone, and androgens) and inhibins' secretion will decrease their plasma concentrations and subsequently the negative feedback on the hypothalamus and pituitary, resulting in an increase in follicle-stimulating hormone (FSH) secretion. The increased FSH secretion may bring about an increased recruitment of preantral follicles to enter the differentiational one way of maturation, being furthermore exposed to the gonadotoxic effect of the alkylating agents, ending in increased, exponential rate of follicular apoptosis and degeneration. This vicious cycle may be interrupted by the GnRH-a administration through its ability to prevent an increase in FSH concentrations.
  2. Another possible explanatory mechanism to the beneficial effect of GnRH-a on decreasing the chemotherapy-associated gonadotoxicity is the decrease in the utero-ovarian perfusion due to the hypoestrogenic state, generated by the pituitary-gonadal desensitization. High estrogen concentrations significantly increased ovarian perfusion and the vessel endothelial area, in a rat model of ovarian hyperstimulation, and this effect was significantly and dose-dependently inhibited by administration of GnRH-a. The decreased utero-ovarian perfusion induced by the GnRH-a, may result in decreased total cumulative exposure of the ovaries to the chemotherapeutic agents as compared to a "control" patient, in a normoestrogenic milieu, thus resulting in decreased gonadotoxicity.
  3. It has been shown that not only rodents, but also primate and human gonads contain GnRH-receptors. In an ovarian carcinoma cell line, GnRH-I and -II receptors' activation may result in decreased apoptosis. Whether the GnRH-a effect is direct on the oocyte cumulus complex, or on the granulosa cell, or possibly on another ovarian compartment in addition to its possible hypogonadotropic effect, is an open question of significant scientific interest. Most recently, proof of a direct effect of GnRH-a, independent of the hypogonadotropic milieu, has been provided by Imai et al., who have shown a direct, in-vitro protection from the doxorubicin induced granulosa cell damage, by a GnRH-a.
  4. Another possibility is that the GnRH-a may up regulate an intragonadal antiapoptotic molecule such as sphingosine-1-phosphate (S-1-P). S-1-P has been shown to prevent chemotherapy inducedgonadotoxicity both in vivo and in vitro. Whether the GnRH-a adjuvant co-treatment positive effect is direct or possibly associated with an intraovarian increase in S-1-P is a question of tremendous scientific interest and clinical impact. It obviously awaits further investigation.
  5. Revolutionary data were presented, whereby mouse ovaries or even bone marrow may possess mitotically active germ-cells that continuously replenish the pool of immature follicles. These germline stem cells (GSC) may exist in the mouse ovary and/or bone marrow and regenerate the primordial follicle pool. These observations contradict the basic doctrine of reproductive biology whereby most mammalian females lose the capacity for germ-cell renewal during fetal life, such that a fixed reserve of germ-cells (oocytes) enclosed within follicles is endowed at birth. One may speculate that the GnRH-a protective effect may possibly be through protection of the undifferentiated GSC, who ultimately generates de-novo primordial follicles. Indeed, the observation of temporary, high, reversible FSH concentrations in a third of our patients, several months after the chemotherapy and GnRH-a co-treatment, even in those who spontaneously conceived later on, may point toward reversible gonadotoxicity. The possible de-novo formation of follicles by the surviving germlinestem-cells brings about a decrease in FSH concentration and return of regular cycles, ovulation, and even gestations. Multicenter, prospective, randomized studies are awaited to substantiate the in-vivo effect of GnRH-a as an unequivocal means for minimizing follicular apoptosis. Most recently, four prospective randomized studies have validated the protective role of GnRH-a in preservation of ovarian function despite chemotherapy in young women. Most relevant to this equivocal and highly debatable issue, a recent publication from one of the previous opponents to GnRH-a use for fertility preservation, reporting that the use of GnRH-a during chemotherapy has also significantly increased the probability to become pregnant [OR = 12.87; P = 0.001]. Most recently, we have also shown that the GnRH-a co-treatment is beneficial not only against regular chemotherapy, but also for lymphoma patients undergoing stem cell transplantation.



  Continous Stimulation During The Follicular And Luteal Phase: A New Algorith For Treatment Of Poor Responders Top


Adrian Ellenbogen

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Technion, Haifa, Israel, E-mail: ellenbogen55@yahoo.com

A poor responder patient was first described in 1983, when 150 IU human menopausal gonadotropins caused a peak estradiol <300 pg/ml and had few eggs retrieved (Garcia et al., Fertil Steril 1983, 39:171). For some woman this is not unexpected. For a young patient who has apparent normal ovarian reserve but respond poorly-her treatment remains a particular challenge regarding ovarian stimulation, oocyte quality and quantity and is associated with low pregnancy rates. According to the Bologna criteria, a poor ovarian response (POR) is diagnosed using minimal criteria of which at least two of the following three features are present: (1) Advanced maternal age (≥ 40 years) or any risk factor for POR; (2) A previous episode of POR (≤3 oocytes with a conventional stimulation protocol). (3) Abnormal ovarian reserve test; Furthermore, two episodes of POR after maximal stimulation are sufficient to classify a patient as a poor ovarian responder (Ferraretti et al., 2011). Women with POR have significantly reduced pregnancy rates (approximately 2-4%) and constitute approximately 9-24% of women undergoing IVF with standard ovarian stimulation (Aghahosseini et al., 2011). Various factors, including decreased ovarian reserve, have been associated with a poor response. However, alterations in intra-ovarian factors or gonadotropin receptor regulation could also contribute to suboptimal response. Additionally, poor responses may result in part from a shortened follicular phase with limited ability to recruit a sizable cohort, or from differential sensitivity of early antral follicles to follicle-stimulating hormone (FSH). Although many protocols have been proposed to increase ovarian response, there is presently insufficient evidence to support the routine use of any particular intervention either for pituitary down-regulation or for ovarian stimulation or adjuvant therapy in the management of poor responders. Flare-up gonadotrophinreleasing hormone agonist (GnRHa), standard-dose flare-up, reduced-dose GnRHa, GnRHa stop GnRH antagonists, recombinant luteinizing hormone administration, luteal initiation of FSH, estradiol in the luteal phase, addition of adjuvant and modified natural protocols will be evaluated, analyzed and discussed. New innovative, pioneering procedures, regarding continuous stimulation during follicular and luteal phase anticipated to improve outcomes in poor responders will be presented, besides new potential biomarkers that may function as an important diagnostic tool for young poor ovarian responders. Fruitful discussion concerning the experience of the audience concerning the treatment of poor responder patients will follow.


  The role of endometrial biopsy in improving implantation rates in in vitro fertilization Top


Ofer Fainaru

Department of Obstetrics and Gynecology, IVF Unit, Hillel Yaffe Medical Center, Technion - Israel Institute of Technology, Israel, E-mail: ofainaru@techunix.technion.ac.il

The success of in vitro fertilization (IVF) and embryo transfer is dependent on a many factors, including patient profile, uterine pathology, stimulation protocols, culture conditions, embryo quality and embryo transfer technique. Implantation is the process of the embryonic attachment to the endometrium and subsequent invasion into the stroma of the uterine wall. It is a complex and multistage process involving a myriad of cytokines and growth factors as well as cross talk between the embryonic tissue and the endometrium. Because implantation failure is frequent, and comprises a limiting step in IVF success, several methods have been suggested to improve implantation rates with inconsistent success rates. One of the most promising methods is local injury to the endometrium. In 2003, Barash et al. were the first to report that endometrial injury before IVF among women with repeated implantation failure was associated with increased rates of implantation, clinical pregnancy and live birth. The findings were supported by subsequent studies. The purpose of my talk will be to examine the association between endometrial injury and implantation, to describe possible mechanisms for this effect and to try and establish clinical guidelines for infertile couples in light of the current evidence.


  Complications of ovarian stimulation Top


Hassan N Sallam

Department of IVF, Alexandria Fertility Center, Alexandria, Egypt, E-mail: hnsallam@link.net

Ovarian stimulation is an integral part of infertility therapy, and although it has been a blessing for many infertile couples who have benefited from its effects, it is not without complications. These include possible immediate complications, possible intermediate complications (during pregnancy) and possible long-term complications. Evidence shows that most of these complications are related to a woman's infertility status and/or increased incidence of multiple pregnancies. Ovarian hyperstimulation syndrome and multiple pregnancies are the two most important immediate complications and can be prevented by proper measures. Besides the stress and anxiety associated with infertility, clomiphene citrate per se has been rarely blamed for mood swings and psychotic illnesses. Other rare immediate complications include adnexal torsion and massive ovarian oedema. Regression analyses have also revealed that fertility drugs are risk factors for ectopic pregnancy as well as preterm birth. Fertility drugs were also found to be risk factors for positron-emission tomography in patients treated with in vitro fertilization (IVF) but not intrauterine insemination or ovulation induction. Clomiphene and letrozole are associated with a slight decrease in birth weight and a slight increase in congenital anomalies, but there is no evidence that letrozole increases the risk of congenital anomalies compared to clomiphene citrate. IVF singleton babies have a higher incidence of perinatal mortality, preterm delivery, low birth weight (LBW), very LBW and for being small for gestational age, but this is not necessarily related to the medication used. Finally, a small study based on a mailed questionnaire found that fertility drugs were associated with early menopause (by 3.5 years), but more studies are needed to confirm this finding. There is no evidence to suggest a direct cause relationship between ovarian stimulation and cancer regardless of the number of treatment cycles or the type of fertility drugs used. The slightly elevated risk of uterine cancer reported in some studies may be because of the women's characteristics including their infertility status.


  Role of vitamin d in impaired fertility treatment Top


Namita Kotia

Department of IVF, Aastha Fertility Care, Jaipur, India,

E-mail: namitakotia2000@yahoo.co.in

Aim: To assess and evaluate the relationship between Vitamin D and fertility in women and men. Method: Systemic literature search and study. Result and Discussion: Vitamin D is a fat soluble steroid hormone having endocrine, paracrine and autocrine functions. Vitamin D receptors and Vitamin D metabolizing enzymes are found in reproductive tissues of male and female, keeping action of Vitamin D not unique to skeletal system but a definitive role in polycystic ovary syndrome, impaired fertility, endometriosis, impaired antiMüllerian hormone and impaired semen parameters.


  Improving intrauterine insemination pregnancy rates Top


Gulam Bahadur

Department of Obstetrics and Gynaecology, NHS Trust Hospitals, UK, E-mail: bahadur.g@gmail.com

Therapeutic intrauterine insemination (IUI) using the husband's sperm is commonly performed for malefactor infertility, as well as, to enhance the probability of conception in various infertility conditions IUI is the most universally practiced procedure in sub fertility treatment. The European in vitro fertilization monitoring program in 2004 reported 98 388 IUI cycles from 19 countries leading to 12 081 births (12.3% per cycle), of which 87% were singleton, and 13% were multiple births (Andersen et al., 2008). Some investigators have questioned the value of IUI for couples about sperm concentration. Confine et al. reported the lowest total motile sperm count at which pregnancy occurs ranges between 1 and 5 × 10 6 sperm. In contrast Brasch et al. found that there was a significantly increased chance for pregnancy whenever the total motile sperm count used for IUI exceeded 20 × 10 6 spermatozoa. The majority of studies attempting to find which sperm characteristics correlated with cycle outcome included multiple female infertility problems. Thus, the results might be biased by the other infertility etiologies that were treated in parallel. The aim of this presentation is to reflect on our experience of improving IUI outcomes while reviewing areas which can improve outcomes and our understanding of patient management to give better results. Unique data will be presented at the meeting which will reaffirm confidence in the IUI procedures and to obviate unnecessarily expensive procedures.


  In vitro maturation of oocytes, results are comparable and may have advantages over standard in vitro fertilization Top


Adrian Ellenbogen

Department of Obstetrics and Gynaecology, IVF Unit, Hillel Yaffe Medical Center, Hadera, Rappaport Faculty of Medicine, Technion, Haifa, Israel, E-mail: ellenbogen55@yahoo.com

Introduction: In vitro maturation (IVM) has advanced significantly from its initial description to its current widespread clinical applications. Despite these advances, however, there are still many controversial issues surrounding this treatment. Given that IVM is an emerging protocol (at least in humans), there are many controversial areas of debate, and especially regarding the subject of the best candidates for IVM; how should we select our patients? Aims: To evaluate the outcome of IVM procedure in perspective with known routine IVF results. Settings and Design: University IVF unit. Materials and Methods: The PubMed database was searched from 1999 to 2013 for publications concerning the indications and results of IVM and to examine the possibility that IVM results may be comparable to standard IVF. Results: In vitro maturation of the oocyte procedure obtained a 35% clinical pregnancy rate in young women, comparable with in vitro fertilization (IVF) in many programs. The IVM obstetrics and perinatal outcome are comparable with IVF/intracytoplasmic sperm injection. The improvement in treatment and protocol has produced good results. Conclusions: In vitro maturation of oocytes is a simple procedure. It is economical and less stressful for women. Puncture is simple and safe. It can avoid short-term complications, such as ovarian hyperstimulation syndrome and long-term complications, such as hormone dependent neoplasms including breast and ovarian cancers. Studies to date have not identified an alarming rate of congenital anomalies in IVM children. IVM holds great promise as an alternative to assisted reproductive technologies and may be the procedure of choice not only for infertile patients but also for obtaining oocytes for donation or fertility preservation. Improving embryonic-endometrial synchrony through pharmaceutical or other manipulation of endometrial/uterine receptivity will hopefully result in future improvements in IVM success rates.


  Social egg freezing Top


Goral N Gandhi, Gautam Allahbadia

Rotunda-Center for Human Reproduction, Mumbai, India, E-mail: wecare@rotundaivf.com

All women share a common dream of becoming a mother. Female fertility begins declining in the late 20's, however conception rates remain high into the 30's. After age 35, the decline accelerates and reaches nearly zero pregnancy potential by the time a woman reaches age 45. In addition, women over 35 have an increased risk of miscarriage and/or genetic abnormalities in their children as a result of age-dependent changes in egg quality. Fertility preservation (FP) is a very fast emerging branch of reproductive medicine, involving the preservation of reproductive gametes and tissues. Cancer patients who are to start chemotherapy or undergo surgery, patients undergoing in vitro fertilization (IVF), women with other medical conditions leading to premature menopause and healthy women who wish to delay their fertility for social, educational or professional reasons are the main beneficiaries of FP strategies. "Social Egg Freezing" is the term given to attempts at FP via egg freezing for nonmedical reasons. Last few years have seen tremendous advancements in the field of cryobiology, with special emphasis on oocyte vitrification. These advancements have greatly changed the way IVF centers operate. Till recently, egg freezing was offered to young, oncological female patients, who are facing chemotherapy or surgery. However, the American Society for Reproductive Medicine at the end of 2012 endorsed oocyte cryopreservation as a standard practice for FP. Some research has suggested that elective egg freezing is a cost-effective method for achieving a future live birth for women under age 39, compared to the possibility of undergoing IVF at a later time in life.

The aim of this presentation is to explore the need and scope of social egg freezing, taking into account.

  • The biological, societal and scientific background.
  • The evidence from the laboratory.
  • The pros and cons.


The concept of egg banking and FP or social egg freezing offers hope to all women who are concerned about their future fertility. It greatly increases a woman's potential to have children later in life.


  Music in the art incubators Top


Esther Velilla Garcia

Department of Embryology, Institute Marques, Center for Embryo Medicine, Barcelona, Spain, The PGD Lab Kuwait, E-mail: esthervelilla@pgdcem.com

Since the start of assisted reproduction, in vitro culture conditions have always tried to mimic the in vivo situation in terms of temperature, light levels, oxygen and carbon dioxide levels and nutrition support. Some studies have also tried to mimic uterine movements. The movement of the oocyte and early embryo from  Fallopian tube More Details to uterus is necessary for successful implantation. However, the movement is also needed for the dispersal of the toxic metabolites created by the oocyte, zygote or embryo, and to be able to obtain the metabolites that they need to be able to develop further (Paria and Dey, 1990; Hill, 2001; Muglia and Motta, 2001). Different approaches have been developed in terms of simulating this natural movement in the laboratory: Use of mechanical microvibrations to embryo culture plates (Isachenko et al., 2010, 2011; Mizobe et al., 2010), use of dynamic fluids in embryo culture (Suh et al., 2003; Cabrera et al., 2006; Smith and Takayama, 2007; Blockeel et al., 2009; Heo et al., 2010; Alegretti et al., 2011; Smith et al., 2011; Swain and Smith, 2011) or use a tilting embryo culture system (Hara et al., 2013). This talk will focus on the use of music as a source of microvibrations in vitro cultures, and how this can improve results in vitro fertilization.


  Egg donation program in a globalized world Top


Esther Velilla Garcia

Department of Embryology, Institute Marques, Barcelona, Spain, E-mail: esther.velilla@pgdcem.com

More than 25 years after the first children conceived by egg donation were born, the reality of egg donation in Spain has changed substantially. Then, it was something exceptional; today it's an increasingly necessary treatment due to the delay of motherhood that makes that more women need the eggs of a young girl to become mothers. The Spanish law of reproduction is one of the most advanced in Europe. This, together with the high level of the clinics' reproductive biology, makes that Spain is the first country in the world, after the United States, in which more egg donation treatments are performed. The cross border reproductive care phenomenon has been possible thanks to a decrease in the price of communications, the phenomenon of low-cost flights, and the new technologies' boom. Internet allows a couple to find out what is the best destination for their treatment and contrast that information in the forums. In the beginning, this phenomenon arose before the prohibition or restriction on certain treatments in some countries. Over the years, the pursuit of medical excellence has become a new reason for couples who decide to seek treatment abroad. Let's take, for example, the case of Europeans that more egg donation treatments perform abroad: The British. According to a report by the European society of human reproduction and embryology cross border reproductive care in six European countries country published in the human reproduction journal in 2010, the reasons for leaving their country are not only legal but respond almost equally to cases of failed treatment, difficulty to access an egg donation and search for medical quality. Couples don't travel only for egg or sperm donation, but many times they do it also looking for a womb for rent. This makes that the clinics adopt new infrastructure and new ways of working in order to respond to an existing need. In this block, we will discuss how we have adapted to the new families.


  Infections in the in vitro fertilization lab Top


Bryan Woodward

IIVF Consultancy Services, UK, E-mail: theeggman68@gmail.com

An in vitro fertilization (IVF) lab should provide an optimal environment for fertilization and development of viable embryos. However, whilst IVF culture systems are designed to promote and sustain optimal conditions for gametes and embryos, they can also provide an ideal environment for infectious micro-organisms to thrive. Infective microbes have the potential to jeopardize the health of gametes and embryos. Furthermore, IVF lab infections can also compromise the treatment of other patients via nosocomial infection. All aspects of an IVF treatment cycle can provide numerous potential sources of microbial contamination, from patients and their biological fluids, fresh and frozen gametes or embryos imported into the lab, staff, visitors, the laboratory environment, air conditioning systems, equipment, consumables, media and imported gases and liquids. This presentation will discuss micro-organisms of clinical importance to the IVF lab, including bacteria, fungi, parasites, viruses and prions. Methods of detection will be covered as well as the most effective policy of containment should infection be introduced. Beware, the information from this presentation could be potentially infectious.


  Troubleshooting: If Anything Can Go Wrong, It Will Top


Bryan Woodward

IVF Consultancy Services, UK, E-mail: theeggman68@gmail.com

Last century, a US engineer called Murphy had problems with his experiments, leading to the conclusion that if anything can go wrong it will. This became known as Murphy's Law, a law that can be applied to many areas, including assisted reproduction. To perform efficient assisted reproduction techniques (ART), all aspects of the fertility clinic must run optimally. When things go wrong, all disciplines should work as a team to come up with solutions as our patients are relying on us to provide high standards of care. This presentation will focus on troubleshooting in the assisted conception laboratory. Examples from many years of troubleshooting in ART will be provided, and there will be a demonstration of how to produce flow charts for a systematic approach to solving problems quickly and efficiently. Murphy was correct that if anything can go wrong it will, but if we keep calm and carryon, then as an effective team, we can work together to troubleshoot any problem!


  Natural Cycle Ivf: A Critical Appraisal Top


Benjamin Fisch

Beilinson Hospital for Women-Rabin Medical Center, Petach-Tikva, and Sackler, Tel-Aviv University, Tel-Aviv, Israel. E-mail: bennyfisch@gmail.com

Natural cycles (NC) were abandoned in vitro fertilization (IVF) (NC-IVF) due to premature luteinizing hormone surges and subsequent high cancellation rates. Over the years, spontaneous cycles have been replaced by controlled ovarian hyperstimulation (COH) combined with gonadotrophin-releasing hormone analogues. However, these stimulation protocols have increased the frequency of ovarian hyperstimulation syndrome (OHSS) and the occurrence of multiple pregnancies which became the major complication of IVF. Consequently, natural cycles have been re-introduced as an alternative to simplify IVF treatment procedure, to reduce its costs, and to avoid the risks of OHSS and multiple pregnancies. However, spontaneous cycles are still rarely used nowadays because of the alleged low pregnancy rates. Natural cycles- in vitro fertilization (NC-IVF) (or modified natural cycle with minimal stimulation) has specifically been proposed for the challenging population of poor responders. Both protocols are less demanding and require a lower dose of gonadotropins compared with the conventional COH treatment. In addition, it has been suggested that this protocol may provide a single oocyte of better quality and thus allow the transfer of a healthier embryo into a more receptive endometrial environment. However, recent studies that examined the effectiveness of NC-IVF in women with poor ovarian response found that live birth rates in women treated with NC-IVF were significantly lower. The results from NC-IVF also indicate that this treatment modality is even less effective in older patients. Several studies demonstrated that very few pregnancies were observed in the NC-IVF group among patients >38 years, and a marked difference in ongoing pregnancy rate/embryo transfer between younger and older patients was observed using 38 years as a cut-off threshold.


  Prompt stimulation protocols for patients with of malignancy Top


Bala Bhagavath

Department of Obstetrics and Gynaecology, University of Rochester Medical Center, USA, E-mail: bala_bhagavath@urmc.rochester.edu

Prompt stimulation protocols can be considered under two broad categories: Those for conventional in vitro fertilization (IVF) and those for in vitro maturation. Protocols for conventional IVF include the random start protocols including late follicular phase, luteal phase following natural ovulation or after human chorionic gonadotropin induced ovulation. Strategies for special situations including estrogen receptor positive breast cancer, hematologic malignancies, polycystic ovary syndrome and comorbidities will be discussed. The overall success rate of these protocols as compared with IVF in non-cancer patients will be discussed for counseling purposes.


  Ovarian Stimulation Strategies For Women With Anti Mullerian Hormone <0.1 Top


Bala Bhagavath

Department of Obstetrics and Gynaecology, University of Rochester Medical Center, USA, E-mail: bala_bhagavath@urmc.rochester.edu

After a brief introduction to anti-mullerian hormone and its reliability in predicting decreased, ovarian reserve, strategies for improving ovarian response to stimulation in women with decreased ovarian reserve will be discussed. The evidence for the effectiveness of strategies including androgen supplementation, growth hormone supplementation, luteal estrogen priming, microdose flare, ultrashort flare and antagonist protocols, antagonist with corifollitropin alfa and highly purified human menopausal gonadotrophin, follicle flushing will be discussed after presenting the evidence available in the literature.




 

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  In this article
Ovarian Torsion ...
An stimulation a...
Sildenafil citra...
Optimizing the g...
Identification o...
Role of vitamin ...
Improving intrau...
Granulocyte colo...
Current methods ...
Ultraviolet air ...
Role of gnrh ago...
Elonva in poor r...
Monitoring of en...
Understanding do...
Time lapse monit...
Recombinant lute...
Impact of ovaria...
Complications of...
Role of vitamin ...
Improving intrau...
Social egg freezing
Music in the art...
Egg donation pro...
Infections in th...
Prompt stimulati...
Recombinant Lute...
Luteal Support P...
The Role Of Lute...
Myomectomy befor...
In vitro maturat...
Human Chorionic ...
Oocyte Cryoprese...
Mild ovarian sti...
Arcuate Uterus A...
Mild Ovarian Sti...
Ovarian Drilling...
Scheduling Gonad...
Corifollitropin,...
Why more is less...
Ovarian Torsion ...
Mild ovar
An stimulation a...
Recombinant Lute...
Luteal Support P...
The Role Of Lute...
Sildenafil citra...
Optimizing the g...
Identification o...
Role of vitamin ...
Myomectomy befor...
Improving intrau...
Granulocyte colo...
In vitro maturat...
Current methods ...
Ultraviolet air ...
Role of gnrh ago...
Elonva in poor r...
Human Chorionic ...
Monitoring of en...
Oocyte Cryoprese...
Understanding do...
Time lapse monit...
Mild ovarian sti...
Arcuate Uterus A...
Mild Ovarian Sti...
Ovarian Drilling...
Recombinant lute...
Scheduling Gonad...
Corifollitropin,...
Impact of ovaria...
Complications of...
Role of vitamin ...
Improving intrau...
IN VITRO MAT...
Social egg freezing
Music in the art...
Egg donation pro...
Infections in th...
Prompt stimulati...
Pragmatic approa...
Evidence Based M...
Is there a role ...
Vitrification: T...
Dopamine agonist...
Ovarian Hyper St...
How to preserve ...
Continous Stimul...
The role of endo...
In vitro maturat...
Troubleshooting:...
Natural Cycle Iv...
Ovarian Stimulat...
Mild Ovar An Sti...
Why 'more is les...
How to preserve ...
Troubleshooting:...
Natural Cycle Iv...
Ovarian Stimulat...
Continous Stimul...
Continous Stimul...
The role of endo...

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