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Year : 2016  |  Volume : 3  |  Issue : 3  |  Page : 128-140

2nd World Congress on Embryo Transfer and Intrauterine Insemination (WETI 2016)

Date of Web Publication21-Apr-2017

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How to cite this article:
. 2nd World Congress on Embryo Transfer and Intrauterine Insemination (WETI 2016). IVF Lite 2016;3:128-40

How to cite this URL:
. 2nd World Congress on Embryo Transfer and Intrauterine Insemination (WETI 2016). IVF Lite [serial online] 2016 [cited 2021 Dec 8];3:128-40. Available from: http://www.ivflite.org/text.asp?2016/3/3/128/204673

  Slow release intrauterine insemination is the way ahead Top

Bryan Woodward

X&Y Fertility, IVF Department, 144a New Walk, Leicester LE1 7JA, UK, E-mail: theeggman68@gmail.com

Intrauterine insemination (IUI) is a low-technology treatment for people with unexplained infertility and mild male factor. The use of IUI as a first-line treatment for unexplained infertility has met with variable success. Over the past decades, there has been renewed interest in “slow release insemination” (SRI) as a method to improve IUI success rates. This method releases washed sperm into the uterus over a 4-h period, compared to conventional IUI (cIUI) release, which is usually completed within 1 min. This presentation will discuss the principles of how SRI might work to improve success rates. Data will be provided from a recent randomized, controlled, crossover study which compared the efficacy of SRI and cIUI.

  Enhanced intrauterine insemination after falloposcopic tuboplasty Top

Aisaku Fukuda

IVF Osaka Clinic, 1-1-14, Nagatahigashi, Higashiosaka-City, Osaka, Japan, E-mail: fukuda@ivfosaka.com

It has been widely accepted that major cause of female infertility is tubal disorder. The narrowest portion of the human fallopian tube, extending from the uterotubal ostium to the ampullary-isthmic junction, is vulnerable to pathogenic organisms. Sexually transmitted diseases and also opportunistic infections with or without medical procedures such as intrauterine operations are considered to be a risk factor. Tubal disorder often causes infertility by occlusion or stenosis. Falloposcopic tuboplasty (FT) is a novel technology for the treatment of tubal patency disorders. FT procedure is the process of transcervical balloon tuboplasty combined with retrograde imaging of tubal epithelial lining. Although assisted reproductive technology (ART) has been used lately for tubal factor as a standard treatment, we apply FT as an initial treatment combined with intrauterine insemination (IUI). Indications for FT are tubal lesions, either unilateral or bilateral tubes affected, without hydrosalpinges. FT treatments could be performed at outpatient clinic under venous sedation with propofol. Patients are followed mainly by IUI for at least 4 months. Overall clinical pregnancy rate after FT is 23.7% at our institution. Pregnancy rate of the patients with unilateral lesion (30.1%) was significantly higher than that with bilateral lesion (22.3%). Average duration between FT and pregnancy was 151 days. More than 80% of pregnancy was achieved within 6 months after FT. Average duration of infertility in the pregnant couples was 3 years 6 months. Pregnancy rate per IUI cycle on the patients of bilateral tubal occlusion after FT was 4.5% which supposed to be 0% due to bilateral occlusion. Ectopic pregnancy rate after FT (1.15%) did not increase compared to non-FT IUI (0.95%). In conclusion, FT could be performed outpatient bases and achieves acceptable pregnancy rate with conventional infertility treatment. IUI accompanied with FT is a strong tool for tubal factor infertility before ART.

  Preparing for the difficult embryo transfer: Tricks learned over 4000 embryo transfers Top

Michael D Scheiber1,2

1IVF Department, Institute for Reproductive Health, 2IVF Department, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA, E-mail: scheibermd@gmail.com

Embryo transfer is a critical part of a successful in vitro fertilization (IVF) cycle. Difficult transfers can detrimentally affect outcomes and cause significant stress for both patients and physicians. Careful preparation in advance of the actual day of embryo transfer can help ensure that transfer is accomplished smoothly. In this talk, an experienced IVF practitioner will discuss techniques and tools to help optimize the completion of potentially difficult embryo transfers.

  In vitro fertilization or intrauterine insemination: What should be the first-line treatment for unexplained infertility? Top

Peter Kovacs

IVF Center, Kaali Institute, Budapest, Hungary, E-mail: peterkovacs1970@hotmail.com

Infertility is defined as the inability to conceive after >1 year of unprotected intercourse. There are multiple etiologies of infertility. Infertile couples typically undergo a basic evaluation that assesses ovarian function, semen parameters, and anatomic structures. It is based on the results, duration of infertility, and the patient's age that a decision regarding treatment can be made. In about 1/4th of the cases, the evaluation will not identify a clear cause for infertility, and these cases could be better described as subfertile cases. In a good proportion of these cases, advanced maternal age is a contributing factor. In other cases further, extended and expansive testing could identify genetic hematologic, immunologic, peritoneal factors that could contribute to infertility. Rather than undergoing an extensive evaluation, a more common approach is to treat these couples; a wide range of treatments can be considered. In younger couples with a relatively short duration of infertility, expectant management may be appropriate. Those with more advanced age may start with in vitro fertilization (IVF) right away. Controlled ovarian hyperstimulation (COH) with various drugs, COH + timed intercourse or intrauterine insemination (IUI), and IVF/intracytoplasmic sperm injection are further options to choose from. When expectant management is compared to COH + IUI, no significant difference in ongoing pregnancy rates (OPR) can be found. When COH using gonadotropins + IUI is compared to COH using clomiphene citrate or aromatase inhibitors + IUI, a higher OPR is observed, but the rate of multiple pregnancies increases as well. Limited evidence has not shown a benefit with IVF over IUI in unexplained infertility. The care of couples with unexplained infertility is challenging as there are very few well-designed studies that provide us guidance. Counseling becomes very important during which the couples need to be explained about natural fertility and how the treatments can be taken to the next level if one method fails. The risk-benefit profile of treatments as well as the associated expenses needs to be considered. Time-to-pregnancy is very important these days with both partners likely to work we need to consider dropout rates as well. During the presentation, the basic infertility workup and the treatment options for those with unexplained infertility will be discussed.

  What is the optimal method of endometrial preparation for frozen embryo transfers? Top

Kemal Ozgur

Antalya IVF, Antalya, 07080, Turkey, E-mail: kemalozg@yahoo.com

Importantly, it has been confirmed in a systematic review that natural or artificial endometrial preparations, with or without gonadotropin-releasing hormone (GnRH) agonist cotreatment, were equally effective in terms of reproductive outcome. However, each of the regimens has strengths and weaknesses in respect to patient satisfaction and clinic effectivity. Natural cycles are regarded by patients to be associated with less discomfort and lower cost while clinics regard them to be associated with increased patient management, increased risk for cycle cancellation, and not suitable for all patients. Artificial cycles, on the other hand, are regarded by patients to be associated with increased discomfort and cost while clinics regard them to be associated with decreased patient management, decreased risk for cycle cancellation, and suitable not only for patients with cycle irregularities but also to be both predictable (i.e., day of embryo transfer) and flexible (i.e., day of embryo transfer). The addition of GnRH agonist cotreatment in both cycle types has been shown to increase cycle security. Cycle security is of great significance if choosing to implement segmented in vitro fertilization (i.e., routine freeze-all). Administering GnRH agonist on the day of embryo cryopreservation was shown to result in a 0% cancellation rate in artificial cycles, with the transfer of frozen-thawed embryos able to be performed 36 days from the day of oocyte retrieval while maintaining a respectable clinical pregnancy rate. With the goal of health of infants being of foremost importance, further study is required to determine whether artificial frozen embryo transfer potentially increases the risk of adverse perinatal outcomes as the result of epigenetic alterations.

  Do's and dont's for optimizing intrauterine insemination results Top

P Uma Devi

Shree Abirami Fertility and Research Center, Coimbatore, Tamil Nadu, India, E-mail: uma.periyaswamy@gmail.com

Intrauterine insemination (IUI) is a common procedure assistive reproductive therapy that is used to facilitate conception in couples having difficulty getting pregnant. By far, this is the artificial insemination method used most often as compared to intracervical insemination, intratubal insemination, and intrafollicular insemination. By passing a catheter through the cervix, sperm are introduced into the uterus. The procedure is both very brief as well as relatively painless.

In general, it is usually recommended to do IUI just before ovulation is set to take place. Six hours is often the time frame given as washed sperm does not live much beyond 6–12 h. Cycles using a single IUI are normally done 36 h after the surge is detected or 36 h after a human chorionic gonadotropin (hCG) injection when a trigger for ovulation is given, while those having two IUIs done will be inseminated between 24 and 48 h after the surge/hCG injection. There may be a slightly increased chance of pregnancy with two IUIs, but the difference is not statistically significant.

The discussion mainly focuses on the salient practical points which have to be borne in mind to improve the success rates of IUI under ideal laboratory conditions.

  Is increased age and long marital life too late to inseminate? Top

Gita Ganguly Mukherjee, Sunita Sharma

IVF Department, Institute of Reproductive Medicine, Kolkata, West Bengal, India, E-mail: drgitagmukherjee@yahoo.com

Intrauterine insemination (IUI) is a simple and noninvasive procedure which can be performed with low cost and with a reasonable cumulative live birth rate. Pregnancy rate with clomiphene citrate induction + IUI is 10%–13% and with gonadotropin stimulation + IUI it is 14%–18%. The clinical pregnancy in IUI is influenced by several factors, and the age of woman is one of the most important predictors of pregnancy outcome. Age is indirect indicator of oocyte number and quality. It is hypothesized that high-quality oocytes are ovulated first, leaving poor-quality oocytes to be ovulated later in life. Another concept claims an age-dependent increase in intracellular oxidative stress, resulting in higher incidence of follicular depletion, and increase risk of aneuploidy and spontaneous abortion with age. It has been reported that pregnancy rate per cycle is 13.7% in women younger than 40, 4.1% for those more than 40, and no live births seen in women after 42 years. Pregnancy rate was also found to be lower in couples with long duration of infertility which is 14.2% below 6 years and 6.1% above 6 years. Our data also suggested similar results with pregnancy rate per IUI cycle of 11.5% in women younger than 40 years compared to 2.4% is women more than 40 years. The current literature supports that in vitro fertilization (IVF) is the best option for a successful ongoing pregnancy in advanced age. Maternal age affects the outcome of IUI but so does of IVF. IVF is expensive. There is an increased risk of preterm, very preterm, low birth weight, very low birth weight, and small for gestational age in singleton pregnancies conceived after IVF/intracytoplasmic sperm injection as compared to IUI. Hence, in country like India where IVF is not affordable by many patients, IUI can be an option in selected older women where acceptable pregnancy rate can be achieved.

  Anti-mullerian hormone and antral follicle count for prediction of intrauterine insemination success Top

Gurkan Bozdag

Department of Obstetrics and Gynecology, School of Medicine, Hacettepe University, Ankara, Turkey, E-mail: gbozdag@hacettepe.edu.tr

Intrauterine insemination (IUI) with controlled ovarian stimulation (COS) is commonly preferred in couples seeking for infertility treatment. Although unexplained infertility is the most frequent diagnosis in patients undergoing COS + IUI, the presence of mild-moderate endometriosis, mild male factor infertility, cervical factor infertility, and single tubal blockage might constitute other indications for that type of treatment. In those kinds of couples, prediction of success with COS is important to compare the available live birth rates with assisted reproductive technologies and individualize the optimal strategy. In this respect, anti-Mullerian hormone (AMH) and antral follicle count (AFC) have been investigated for their validity in the prediction of success rates. According to limited data, it might be mentioned that AMH and AFC might be used to predict ovarian response and success rates. However, retrospective nature of those studies and limited sample size should be considered as main drawback of the available data.

  Role of frozen-thaw embryo transfer cycle in improving endometrial thickness and pregnancy rate after intracytoplasmic sperm injection Top

Kundan Vasant Ingale, Kundan Ingale, Anjum Shaikh

Nirmiti Clinic, Pune, Maharashtra, India, E-mail: drklingale@yahoo.com

Objective: (1) To compare pregnancy rate between fresh embryo transfer (ET) and frozen-thaw ET (FET) cycles (2) To measure difference in endometrial thickness between initial ovarian stimulation cycle and subsequent FET cycle. Design: This was a prospective randomized controlled, single-center study. Materials and Methods: Ninety-nine intracytoplasmic sperm injection (ICSI) cycles done at Nirmiti Clinic, a center for assisted reproduction at Pune, India, between January 2015 and August 2016, were involved in this randomized controlled trial. All patients were randomly selected to undergo fresh ET (n= 55 patients) and FET cycles (n = 49 patients). In all cycles, ovarian stimulation was done by antagonist protocol. In FET cycles, all embryos were vitrified on day 3. Subsequently, down regulation was achieved with gonadotropin-releasing hormone agonists Depot 3.75 mg IM on day 2 of menses. Endometrium was prepared by starting dose of oral estradiol valerate or estradiol hemihydrate 4 mg/day from the 22nd day of menses and escalated by 2 mg every 3rd day till endometrial thickness reaches to >8 mm with color Doppler subendometrial (zone III) vascular signals showing pulsatility index <1.25 and refractory index <0.6. All cycles undergone day 5 blastocyst transfer after luteal phase support with vaginal progesterone and oral dydrogesterone. In all FET cycles, endometrial thickness was measured on the day of human chorionic gonadotropin in initial ovarian stimulation cycle and on the day of starting progesterone in subsequent FET cycles. Pregnancy rate was calculated in fresh ET and FET cycles. Results: Overall pregnancy rate in 104 ICSI cycles was 56.7% (56/104). Implantation rate per ET and per embryo transferred was significantly higher in FET group than fresh ET group (67.34% vs. 47.27%, P = 0.0391; 40.3% vs. 29.92%, P = 0.0477, respectively). Clinical pregnancy rate was definitely much higher in FET cycles than fresh ET cycles, but it was not statistically significant difference (61.22% vs. 43.63%, P = 0.0731). Endometrial thickness in subsequent FET cycle was more than ET in initial ovarian stimulation cycle by mean 1.84 mm, which was significant. Conclusions: Our results conclude that pregnancy rates are significantly higher in FET cycles than fresh ET cycles, possibly due to improved endometrial receptivity by increasing endometrial thickness in FET cycles. Hereby, we recommend FET cycles than fresh ET cycles to achieve better pregnancy rates. For thin endometrium patients during in vitro fertilization stimulation, better to freeze all embryos and transfer them in subsequent FET cycle to optimize results where endometrium is prepared by exogenous prolonged estrogen administration in a downregulated cycle. We recommend to test this hypothesis by doing large size studies in future.

  Modified natural protocol seems superior to natural and artificial protocols for preparing the endometrium in frozen embryo transfer cycles Top


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

Although several studies claim higher success rates in natural cycle (NC) and modified NC (MNC) protocols, currently, there is little consensus on the most effective method of endometrial preparation before frozen embryo transfer (FET). We conducted this retrospective cohort study to compare the clinical efficacy of NC, MNC, and artificial cycle protocols. Medical records of all patients enrolled in FET cycles between November 2015 and July 2016 were reviewed. Group I (#46) included patients who underwent artificial endometrial preparation, Group II (#8) confined patients enrolled in MNC, and Group III (#12) included patients who had NC protocol. Main outcome parameters were clinical pregnancy, implantation, and miscarriage rates. NC and MNC are more patient friendly compared to artificial cycle. Although there was a tendency toward higher implantation and pregnancy rates in MNC protocol, the difference did not reach statistically significant level. The study is ongoing, and larger sample size may reveal a significant difference. Miscarriage rates were similar for the three groups. The limitations of our study are the retrospective design and small sample size in MNC and NC groups. Balance of the existing studies does not reach a consensus on the most effective method of endometrial preparation before FET. The results of our study will certainly provide a contribution to the existing knowledge in the literature. In addition, our study is unique as revealing the first data from Turkey comparing different endometrial preparation protocols.

  The effect of interval from semen collection to intrauterine insemination: Does it matter? Top

Neelam Ohri

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

Intrauterine insemination (IUI) is widely practiced modality for infertility treatment. Despite all efforts, success rate has not reached beyond 16% pregnancy rate/cycle. The variation in success rate is very high as there are many variables for success such as different age groups, different causes of infertility, different treatment protocols such as the nature of induction of ovulation, the capacity of processing the semen in the laboratory, and insemination techniques involved in different studies. Regarding place of semen collection, i.e., clinic versus home may matter. The WHO[1] recommends that ideally, the male partner should produce the semen specimen in a private room near the laboratory for better assessment of liquefaction of the ejaculate and to prevent its exposure to extremes of temperature as progressive sperm motility of a freshly ejaculated semen specimen declines with time and exposure to extremes of temperature. However, the WHO recommended limit of interval of 1 h maximum from semen collection to its delivery to the laboratory relates to “diagnostic semen analysis” only and should not be applied to “therapeutic semen processing” for clinical procedures such as IUI and IVF. Two studies related with semen analysis observed that semen samples collected by masturbation at home had a higher count and motility than those collected in the clinic. Authors suggested that this observation could be taken into consideration in infertility treatment. [2,3] It was interesting to note that the type of ovarian stimulation could affect the result in relation to place of collection. Yavas et al.[4] in their retrospective study concluded that ovarian stimulation with human menopausal gonadotropin (hMG) but not with clomiphene citrate (CC) resulted in better pregnancy rates when semen was collected at the clinic. There is ongoing debate whether the time factor can affect sperm quality. There are three time intervals: (1) time interval between semen collection and sperm wash (SW), (2) SW and insemination, and (3) total time from collection to insemination. If collection to SW interval is more, sperms are exposed to a prolonged postejaculation seminal environment. It may result in irreversible prevention of capacitation and hence of acrosome reaction since seminal plasma contains decapacitation factor(s). There is also risk of prolonged exposure to free radicals such as seminal leukocytes and immature and/or abnormal spermatozoa with residual cytoplasm. Shimuzu et al.[5] assessed the relationship between the time interval from semen collection to SW and IUI outcome; 1054 IUI treatment cycles were analyzed. The time interval from semen collection to SW was divided into three groups: (a) <3 h, (b) 3–5 h, and (c) over 5 h. Total pregnancy rate was 14%, and IUI pregnancy rate was not different between groups. Another study was done by Alexander et al.[6] to correlate pregnancy outcomes with the subject time intervals in 210 CC-IUI cycles. Mean intervals from collection to sperm washing, from sperm washing to IUI, and from collection time to IUI were similar in pregnant and nonpregnant CC-treated women. A study conducted by Yavaş and Selub[4] in 2003 analyzed 132 IUI cycles to determine if IUI outcome was affected by intervals from semen collection to SW , from SW to IUI time, and from semen collection to IUI time. Pregnancy was not affected by these intervals in CC-treated women but was associated with shorter intervals in hMG-treated women. Intervals of semen collection-SW, SW-IUI, and semen collection-IUI were shorter in pregnant than in nonpregnant hMG-treated women. Semen washed within 30 min after collection resulted in a higher pregnancy rate than that processed 31–60 min after collection in hMG-treated but not in CC-treated women. IUI performed within 90 min after collection resulted in a higher pregnancy rate than IUI performed at 91–120 min or >120 min after collection in hMG-treated but not in CC-treated women. Delaying semen processing from 30 min up to 1 h and/or delaying IUI from 90 min up to 2 h after collection compromises the pregnancy outcome in hMG-IUI cycles. Semen specimens should be processed as soon as just after liquefaction and within 30 min of collection, and IUI performed as soon as just after processing and within 90 min of collection. Since long, it was proposed that spermatozoa for clinical procedures such as IVF, gamete intrafallopian transfer, or IUI and for the laboratory test of sperms fertilizing ability must be separated from the seminal environment as soon as possible after ejaculation.[7] There are few concerns regarding prolonged SW-IUI interval as washed and capacitated motile spermatozoa may lose their fertilizing capacity. Another concern is exhaustion of energy sources in the sperm washing medium by the motile spermatozoa during a prolonged SW-IUI interval. Because sperm motility requires energy sources, such as glucose and fructose,[8] washed motile spermatozoa deprived of energy sources during a prolonged SW-IUI interval might not be able to reach the fertilization site in fallopian tubes after IUI. Another concern could be of premature (in vitro) capacitation of washed motile spermatozoa in the sperm washing medium during a prolonged SW-IUI interval because (a) seminal decapitation factor(s) are removed along with seminal plasma during the SW procedure and (b) capacitation occurs spontaneously in simple defined medium, implicating a potential role of autocrine induction.[9] Thus, washed motile spermatozoa that have undergone in vitro capacitation prematurely relative to fertilization time, during a prolonged SW-IUI interval might not be able to undergo subsequent changes in the female reproductive tract after IUI. It was found that if washed sperm can be incubated for a minimum of 30 min at 37°C, the pregnancy rate is optimum though a longer period up to 180 min also did not compromise the pregnancy rate.[10] Another study demonstrated that sperm parameters are negatively affected from prolonged incubation time. A maximum 60-min limit of the interval between the onset of the postwash sperm incubation and IUI time increased pregnancy rates.[11] Considering the place and temperature for sperm incubation to avoid premature capacitation of sperms, few studies suggest that human sperm incubation at room temperature does not allow capacitation. This blocking effect is over come when spermatozoa are exposed to 37°C, and washed spermatozoa undergo capacitation in response to human follicular fluid when incubated overnight at 37°C.[12] Another study indicates a significantly better and longer preservation of sperm quality when incubation is performed at room temperature. These findings may convince laboratories to change the routinely used sperm storage conditions to maximize the quality of the prepared sperm sample.[13] The debate goes on. Until we have more prospective randomized trials, to maximize IUI pregnancy outcome not only should semen specimens be collected at clinic to assess liquefaction and documentation but also be processed as soon as just after liquefaction and within 30 m of collection and also IUI be performed as soon as within 90 m of semen collection.

  References Top

  1. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Switzerland, Geneva: WHO Press; 2010.
  2. Saad Elzanaty, Johan Malm Fertil Steril. 2008;89:1718-22.
  3. Wang W, Zhong ZM, Su N, Peng YY, Huang TT. Fertil Steril 2014;20:995-8.
  4. Yavas Y, Selub MR Fertil Steril 2004;82:1638-47.
  5. Shimuzu Y, Yorimitsu T, Motoyama H, Ohara M, Kawamura T. Fertil Steril 2009;92:145.
  6. Alexander CJ, King J, Lipari C, Zhao Y, Wallach EE. Fertil Steril 2005;84:279.
  7. Mortimer. Human Reprod 1998;13:2139-46.
  8. Williams AC, Ford WC. J Androl 2001;22:680-695.
  9. Wu C, Stojanov T, Chami O, Ishii S, Shimizu T, Li A. J Biol Chem 2001;276:26962-8.
  10. Esra B. Kilicdag, J Turk SOG 2012;9:159-63.
  11. Koyun E. J Turk Ger Gynecol Assoc 2014;15:82-5.
  12. Marin-Briggiler CI, Tezon JG, Miranda PV, Vazquez- Levin MH. Fertil Steril 2002;77:252-9.
  13. Thijssen A. July 2012 GIFT, South Africa.

  The influence of the depth of embryo replacement Top

Aisaku Fukuda

IVF Osaka Clinic, 1-1-14, Nagatahigashi, Higashiosaka-City, Osaka, Japan, E-mail: fukuda@ivfosaka.com

Assisted reproductive technology (ART) has been applied for the treatment of infertility for more than 38 years. Traditionally, little attention has been focused on embryo transfer. It is often viewed as an unimportant variable in the success of an ART cycle. Embryo transfer requires the joint efforts of the embryologist and the clinician. Of course, embryo transfer fails, and there are no healthy embryos that can implant. Likewise, the work of embryologists to maintain the viability of embryos is futile if embryo transfer is unsuccessful. Many factors have been proposed to explain the disparity between embryo transfer and pregnancy rates. Pregnancy rate is not 100% even with genetically normal embryos selected by preimplantation genetic screening. Therefore, inefficiency of embryo implantation may stem from embryo transfer technique. The depth of the embryos to leave, individual difference of clinician or embryologist, and so on have all been supposed to be associated with unsuccessful outcome. Despite the great advances in in vitro fertilization in the past, little has changed in embryo transfer. The goal of transcervical embryo transfer is to deliver embryos to the uterine fundus in a gentle and atraumatic manner. The use of a pretransfer trial, ultrasonographic guidance, cervical lavage, and soft catheters appears to increase the chance of a successful outcome. Fastidious attention to the many details of embryo transfer technique appears to be important for ART successful outcome. In this presentation, not only the depth of embryo replacement but also analyses of the methods of embryo transfer, endometrial preparations for frozen-thawed embryo transfer and clinical outcome, ultrasonography patterns of endometrium at transfer and pregnancy, effectiveness of cervical dilatation before transfer, and more are reported. Moreover, some difficult cases are presented. In conclusion, elaboration of embryo transfer is critical to improve clinical outcome of ART.

  Human embryo cultivation in melatonin containing medium Top

Kirienko Konstantin1, Apryshko Valentina1,2, Kharitonova Margarita1, Troshina Maria1, Ermilova Irina1, Khryapenkova Tatyana1, Voronich Natalia1, Strashnova Aglaya1, Biryukov Alexey1, Bolt Anton1, Klepukov Alexey1, Mironova Anna1, Naumova Anna1, Simonenko Ekaterina3, Yakovenko Sergey1,3

1AltraVita IVF Clinic, 2IVF Department, Faculty of Biology, Lomonosov Moscow State University, 3Department of Biophysics, Lomonosov Moscow State University, Moscow, Russian Federation, E-mail: naumo.ann@yandex.ru

Introduction: Melatonin has been used to improve oocyte maturation and embryo development in vitro in different species (bovine, porcine, and mouse). This study determined the effects of melatonin on in vitro human embryo development, in particular, cleavage and blastocyst rate. Objective: The aim of this study is to compare the effectiveness of human embryo cultivation in medium with different melatonin concentration. Design: Prospective cohort study. Sibling embryos were randomly assigned to culture in control and melatonin supplemented medium. Methods: In this study, embryos obtained from 128 couples undergoing intracytoplasmic sperm injection or intracytoplasmic morphologically selected sperm injection were distributed between culture media LifeGlobal (total number of embryos – 1074), LifeGlobal + 10−9 M melatonin (total number of embryos – 540), and LifeGlobal + 10−6 M melatonin (total number of embryos – 425). Those 128 couples aged between 22 and 41 (the average woman age was 31.4) were neither suffering from genetic diseases nor bearing cryptozoospermia. The resulting blastocysts were used either for embryo transfer or cryopreservation. Results: The study results are presented in the [Table 1].
Table 1: Results

Click here to view
Conclusions: Our study did not reveal statistically significant differences in effectiveness of human embryo cultivation in melatonin or nonmelatonin medium.

  Does velocity of expulsion of embryos make a difference to success rates? Top

Bala Bhagavath

University of Rochester Medical Center, Rochester, NY, USA, E-mail: Bala_bhagavath@urmc.rochester.edu

Embryo transfer is the culmination of the process of in vitro fertilization (IVF). Although simple to execute, it is a crucial step that ultimately determines the success of the IVF cycle. Only one-third of patients receiving embryos ultimately become pregnant, and the suggested reasons for failure in the rest of the cases are many including the type of catheter, the presence of blood on the tip of catheter, lack of concomitant monitoring with ultrasound and incorrect placement of the tip of the catheter in the endometrial cavity, and lack of withdrawal of the catheter a touch before expelling the embryo as well as too fast an expulsion of the embryo from the catheter. The speed of expulsion of embryo from the catheter has not been studied much. Studies in the laboratory have demonstrated increased dynamic pressure and shear stress on the embryo with increased speed of expulsion of the embryo. A recent randomized controlled trial has shown that controlled injection speed while expelling the embryo increases the pregnancy rates. Limited numbers of studies suggest that the velocity of expulsion of embryos has on impact on the pregnancy rate.

  What's the best treatment for cancer patients who freeze their sperm? Top

Bryan Woodward

X&Y Fertility, IVF Department, 144a New Walk, Leicester LE1 7JA, UK. E-mail: theeggman68@gmail.com

Cancer survival rates have drastically improved over recent years, due to advances in diagnostic techniques and therapies. The male reproductive tract remains highly susceptible to chemotherapy and radiation therapy, such that spermatogenesis can permanently be halted. This presentation provides a summary of pathways for sperm banking and explores the best fertility treatments to use the frozen sperm in assisted reproduction. A review of the multidisciplinary team approach will be given to show how education of patients and all members of the medical team can help to provide the most efficient fertility preservation in a timely manner.

  Is in vitro fertilization-embryo transfer better than intrauterine insemination as an initial therapy for unexplained infertility? Top

Bryan Woodward

X&Y Fertility, IVF Department, 144a New Walk, Leicester LE1 7JA, UK. E-mail: theeggman68@gmail.com

In the UK, the National Institute for Health and Care Excellence (NICE) recommended that people with unexplained infertility should be directed to in vitro fertilization (IVF) as a first-line treatment for unexplained infertility, rather than to intrauterine insemination (IUI) (NICE Guideline CG156, 2013). This followed their review which concluded that there was a lack of robust evidence to show the efficacy of IUI treatment over expectant management. The NICE proposal to offered IVF over IUI was highly controversial and rejected by many professionals, such that it led NICE to reconsider its decision. This presentation will look at the evidence that NICE used to guide its decision-making process. Further evidence will be provided that demonstrates that if performed correctly, IUI can provide significant economic benefits over IVF while achieving satisfactory success rate. IUI might also be preferred to IVF as it is a less invasive procedure, avoiding surgery or anesthesia, and reducing the amount of fertility drugs required.

  Difficult embryo transfer: Strategies that help Top

Vishvanath C. Karande

President, Medical Director, Director IVF Program, Infertility Department, InVia Fertility Specialists, Hoffman Estates, Illinois, USA. E-mail: vkarande@aol.com

The word “difficult” is an adjective that means “needing much effort or skill to accomplish.” In practical terms, it means difficulty for a soft embryo transfer (ET) catheter to gain access to the uterine cavity requiring (1) use of a tenaculum, (2) requiring cervical dilatation, or (3) blood around the catheter tip or in the catheter lumen. It is generally accepted that a difficult ET is associated with a lower pregnancy rate. The incidence of difficult ETs varies, however, up to one-third of ETs have been reported as being difficult. A difficult ET can be expected in the following cases: (1) suspected cervical stenosis, for example, h/o cervical conization; (2) acutely anteverted or retroverted uterus, especially in cases with severe endometriosis; (3) false passage in cervix due to previous attempts; (4) uterine anomalies, for example, unicornuate uterus; (5) Ultrasound abnormalities, for example, cystic lesions around cervical canal, endocervical polyps, acute cervicouterine angle. Strategies that help include as follows. (1) Use of trial transfer. We do these with a full bladder under ultrasound guidance, especially in patients with difficulty in gaining access to the cavity during a hysterosonogram, hysterosalpingogram, or at time of intrauterine insemination. (2) Cervical dilatation – regular or use of Dilapan or laminaria tents. Ideal time for dilatation and the risks of using hygroscopic dilators will be discussed. (3) Hysteroscopic resection. Use of the hysteroscope itself, graspers, scissors, Versapoint electrode, and resectoscope will be discussed. (4) Preoperative stitch on the cervix that can be used instead of a tenaculum. This can be inserted at time of egg retrieval. Tubal transfer and transmyometrial ET are beyond the scope of this presentation. Using these strategies, it is possible to dramatically reduce the incidence of unexpected difficult ET and improve pregnancy rates.

  Preimplantation genetic screening: Updated results Top

Esther Velilla

Reproductive Genetic Service, Genetics Department, 4th Ring Road, Jabriya Medical center, 6th Floor, Jabriya Block 1A, Kuwait, E-mail: esthervelilla@thepgdlab.com

Preimplantation genetic diagnosis has been widely used in assisted reproduction for aneuploidy screening (preimplantation genetic screening [PGS]) to select the embryos with a normal chromosome set and, thus, the highest implantation potential for the development of a term pregnancy. A high percentage of embryos generated in in vitro fertilization (IVF) are chromosomally abnormal. Most chromosomal alterations are incompatible with embryo implantation and the development of a term pregnancy, and therefore, this could adversely affect pregnancy outcome. In fact, most of the trisomies are detected in fetuses from the analysis of miscarriages. Moreover, PGS is also used to select the best embryo for transfer. This could adversely affect IVF pregnancy outcome. Although some of the chromosomal abnormalities are incompatible with embryo implantation, others can achieve pregnancy, giving rise to miscarriages and, in some cases, to aneuploid liveborn. In fact, about more than 50% of early miscarriages have chromosomal abnormalities, being trisomies the most frequently detected. PGS can be used to select euploid embryos in order to increase pregnancy and take-home baby rate and reduce miscarriage rate as well as the risk of therapeutic abortion of an aneuploid fetus. To maximize pregnancy rates in infertile couples, most IVF cycles involve the transfer of more than one embryo. However, one of the major drawbacks of multiple embryo transfer is the risk of multiple gestation and its associated pregnancy complications. For that reason, most IVF clinics have considerably reduced the number of embryos transferred at the same time by the use of PGS. The most frequent indications of the realization of IVF-PGS are recurrent miscarriage, more than 2 unsuccessful IVF cycles, advanced maternal age, infertility due to a male factor, and previous pregnancy with a chromosomal abnormality. The key success in a PGD program is due to different factors such as type of patients included, IVF culture conditions, embryo biopsy (day of biopsy and quality), number of chromosomes tested (from 3 to 24), PGD technology used, and embryo transfer. During this talk, we go through each of these different steps and analyze pros and cons to have a wide idea of which PGS program can be applied to our center. In addition, we review the last published clinical results after PGS with comprehensive chromosome screening.

  The analog-analog combination: A novel approach to avoid ovarian hyperstimulation syndrome and enable fresh embryo transfer in high responders Top

Itai Bar-Hava1, 2, 3

1Women' s fertility Center, Ramat Aviv, 2Department of Obstetrics and Gynecology, Assuta Medical Center, 3Wolfson Medical Center, Holon, Israel, E-mail: barhava@gmail.com

It is well known that the administration of human chorionic gonadotropin (hCG) for final oocyte maturation has the drawback in high-responder patients of promoting ovarian hyperstimulation syndrome (OHSS) due to synthesis of vasoactive substances, and a prolonged half-life. Gonadotropin-releasing hormone agonists (GnRHa) have been introduced in gonadotropin-releasing hormone (GnRH) antagonist cycles as an alternative to hCG triggering for final oocyte maturation, in order to avoid this life-threatening complication in high responders. Its main disadvantage is significantly lower pregnancy rates in comparison to that of hCG triggering. Several methods had been described to try and overcome this disadvantage with variable success rates. Our aim was to study an alternative approach of luteal phase support following GnRHa administration for high responders while enabling fresh embryo transfer within the same cycle. This approach comprised daily, continuous administration of GnRH analog for luteal phase support. We hereby present 46 separate cases of patients with high risk to develop OHSS. These patients were administered a GnRHa ovulation trigger to avoid OHSS, followed by continued 2 weeks period of daily intranasal GnRHa (nafarelin) for luteal phase support. No additional progesterone supplementation was administrated. We obtained 24 (52.1%) ongoing clinical pregnancies. None of the patients developed OHSS. Intranasal daily GnRHa is effective in achieving luteal phase support in high-responder patients triggered with GnRH analog for oocytes retrieval while avoiding OHSS.

  How do we achieve the best possible reproductive outcomes: Freeze-all with comprehensive chromosome screening? Top

Kemal Ozgur

Antalya IVF, Antalya, 07080, Turkey, E-mail: kemalozg@yahoo.com

Parallel innovations in laboratory technologies and procedures over the last decade have seen the reproductive outcomes of in vitro fertilization (IVF) improving significantly. In vitro culture technology innovations have led to increased blastulation rates and as a result blastocyst transfers, with a concomitant increase in reported implantation rates. Cryopreservation technology innovations have led to the reporting of survival rates consistently >90%, with the use of vitrification. Comprehensive chromosome screening (CCS) innovations have led to clinically recognizable error rates of <0.5%, with single embryo transfers (ETs) of screened embryos resulting in live birth rates equivalent to multi-embryo ETs of unscreened embryos. Importantly, the increased survival rates of developmentally competent vitrified-warmed blastocysts have resulted in the increased use of frozen ETs (FETs), with implantation and live birth rates reported to be at least equivalent to those of fresh blastocyst transfers. With the reproductive outcomes of FET no longer inferior to those of fresh ET, clinicians have the opportunity to investigate how to exploit the benefits (i.e., endometrial receptivity) of FET and the optimal scheduling of procedures for transferring all embryos into physiologically normal intrauterine conditions of FET. The freeze-all strategy known as segmented-IVF has been purported to be a viable alternative to conventional IVF, especially if any condition resulting from controlled ovarian stimulations has the potential to adversely affect the reproductive outcomes of fresh ET. Moreover, by combining blastocyst culture, blastocyst CCS, blastocyst vitrification, and blastocyst, FET may achieve the best possible live birth outcomes in IVF.

  Waiting times after intrauterine inseminations: What do we know? Top

Michael D Scheiber1,2

1IVF Department, Institute for Reproductive Health, 2IVF Department, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA, E-mail: scheibermd@gmail.com

Busy infertility practices perform hundreds of intrauterine inseminations (IUIs) in any given year, yet there are no uniform recommendations for post-IUI waiting times. There are several conflicting studies in literature, and more research needs to be done. This talk will summarize the existing data. While postembryo transfer wait times are clearly decreasing, the same may not be ideal for optimizing IUI therapy.

  Can embryo catheter loading have an influence on the incidence of ectopic pregnancy in in vitro fertilization/embryo transfer cycles? Top

Mohamed El-Shmoury

IVF Laboratory Director, IVF Department, Villa 37, 65b St, Al Wasl Road, Jumeirah 1, P.O. Box 72960 Dubai, United Arab Emirates, E-mail: mohamad.shmoury@fakihivf.com

Compared with natural conception, ectopic pregnancy (EP) rate is 2.5–5 fold higher after in vitro fertilization (IVF)/embryo transfer (ET). ET technique is the last stage of a series of complementary processes leading to success or failure of an IVF cycle. Among the different steps in ET technique, less attention has been given to the embryo loading (EL) procedure. Although the EL technique looks simple, it is a delicate step in ET. In the present retrospective study, we questioned whether the column of the embryo-containing medium may affect the incidence of EP. A total of 1385 women were subdivided into two groups: Group I (715 patients) and Group II (670 patients). In Group I, the embryo catheter loading technique was “the standard protocol.” In Group II, the loading technique was “the modified protocol.” The main outcome measure was the EP rate. Our results showed that 15 patients were diagnosed with EP (12 in Group I and 3 in Group II). The incidence of EP was significantly lower with the modified technique compared to standard technique (0.9% vs. 3.6, P = 0.03). Our results showed that there is an association between the incidence of EP and the procedure for embryo catheter loading. We assume that both, the gentle embryo deposition due to the presence of a column of free medium which acts as a buffer shoulder against forcible ejection and the absence of air brackets, may minimize the embryo migration inside the uterine cavity which could be an explanation for the lower incidence of EP reported with the modified protocol for EL.

  The benefit of time-lapse observation of embryos during in vitro fertilization: Results of randomized controlled trials Top

Peter Kovacs

IVF Center, Kaali Institute, Budapest, Hungary, E-mail: peterkovacs1970@hotmail.com

In vitro fertilization is considered successful when a healthy full-term baby is born. It is a long process of multiple steps of selection until this goal can be achieved. In a typical cycle, multiple follicles are recruited, about 90% of them provide eggs and about 60%–70% of them fertilize. Typically, 50% of fertilized oocytes turn into good quality embryos, and depending on age, 30%–80% of embryos turn out to be aneuploid. Ultimately, about 10%–40% implantation and around 30% clinical pregnancy rates can be expected. This also means that 85%–90% of the embryos created will never implant. There is an increasing role for the embryologist in this process to identify the embryo with the highest implantation potential. Currently, the standard selection method relies on daily observation under light microscope by removing the embryos from the incubator. Pronuclear morphology, cleave patterns, cell symmetry, fragmentation, and blastocyst morphology are assessed. This snapshot evaluation provides us with limited information only. Time-lapse embryo monitoring allows us to continuously observe the embryos without the need to remove them from the optimal culturing conditions. Significantly more information can be gained about cleavage kinetics, dynamic changes of morphology, abnormal cleavage events, blastocyst morphology, and dynamics. The question is, whether this extra information aids embryo selection? Multiple, mostly retrospective, studies evaluated cleavage times, cell cycle durations, and morphologic changes in embryos that implanted and embryos that failed to implant (embryos with known implantation potential). Based on the most important parameters, algorithms were built that are supposed to help selection. Some of the algorithms favor early kinetic markers, others found late kinetic markers to be predictive, and yet others incorporated morphology in their model. Even the same group identified various markers to be predictive when different patients or different clinics were involved in the studies. It has been suggested that each clinic should build their own model that could be difficult for smaller clinics. Still only limited randomized controlled trial (RCT) data are available that studied the benefits of these models.

During the presentation, time-lapse technology, various predictive kinetic/morphologic markers, and available retrospective/RCT data using time-lapse technology will be reviewed.

  Modified natural cycle in vitro fertilization combined in vitro maturation for treatment of infertility Top

Seang Lin Tan1,2, Rabea Youcef Khoudja2, Justin Tan3, Michael Dahan1,2

1Department of Obstetrics and Gynecology and REI, Division of REI, McGill University, 2OriginElle Fertility Clinic and Women Health Centre, Montreal, 3Department of Obstetrics and Gynecology, University of British Colombia, Canada, E-mail: kykk888@gmail.com

In vitro fertilization (IVF) today is a very successful treatment with live birth rates/cycle exceeding that of spontaneous conception in healthy fertile women, and in the last 20 years, pregnancy rates have continued to improve such that the live birth rate/cycle started today may exceed 50% in women under the age of 35. However, these good results are achieved in the expense of increased multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). Although a number of studies have shown that the use of the antagonist protocol with agonist trigger will reduce significantly, the risk of OHSS fresh embryo transfer (ET) with the addition of a small dose of rescue human chorionic gonadotropin (hCG) still increases the risk of OHSS, while in extreme cases, even freezing of all embryos may result in OHSS. The only way to prevent OHSS completely is if ovarian stimulation is not done. In 1999, we published our first results of in vitro maturation (IVM) showing that we are able to get over 80% maturation rate of germinal vesicle (GV) oocytes collected and a 40% live birth rate/cycle started. Today, IVM can be done for many indications including patients at high risk of OHSS, previous poor responders, or poor quality embryos for no obvious reasons, as an alternative to follicle stimulating hormone (FSH)/human menopausal gonadotropin intrauterine insemination (IUI), and also for fertility preservation. In IVM treatment cycle, withdrawal bleeding is induced and an ultrasound (US) is performed to identify the number of follicles in the ovaries since IVM pregnancy rate correlates directly with the number of oocytes retrieved; US is repeated when the endometrium thickness is expected to be 8 mm and the largest follicle is between 10 and 14 mm, and on that day, hCG 10,000 IU is given and oocyte pickup (OPU) is performed in 38 h later, and in over 10 years, treating >1000 IVM cycles, we never observed a single case of OHSS. The method of doing egg collection is similar to that for IVF egg collection; except 19-gauge single-channel tapered needle is used, more recently, a new needle Steiner-Tan double lumen needle has shown improved results compared to regular egg collection needles. As many as 125 oocytes can be collected in early stimulation, early trigger, modified natural cycle IVF-IVM. The complication rate and pain scores rates of IVF and IVM eggs collection are comparable, and MII which are collected are fertilized using intracytoplasmic sperm injection. Patients receive estrace (micronized estradiol 17 β) following egg retrieval and progesterone following intracytoplasmic sperm injection (ICSI) in divided doses depending on ET (<6 mm, 12 mg of estrace/6–8 mm, 8–10 mg/≥8 mm, 6 mg of estrace in divided doses by mouth), and we have achieved over than 50% of pregnancy rate/cycle in women up to 40 years; IVM has comparable miscarriage rate as IVF and ICSI. Recently, Chian et al. have reported 1421 infants conceived with IVM oocytes, and the incidence of congenital malformations is comparable of healthy pregnancies

. Because aneuploidy rates increase with age, the use of IVM combined with preimplantation genetic screening (PGS) may allow pregnancy rates to remain relatively high even with older patient, but we require serial vitrification of the embryos or eggs from several cycles to have enough embryos to be tested by PGS. There is comparable chromosomes abnormality rate between IVF and IVM embryos. Because FSH/IUI requires 3–4 US scan, 7–10 injections, and the clinical pregnancy rate is 15%, multiple pregnancy rate around 25%, and costs about US$ 1500–2000 for treatment while IVM only requires 2 US scans, 1–4 injections, one OPU, and one ET with a pregnancy rate of between 30% and 50%, and much lower multiple pregnancy rates, IVM should be considered now as the first-line treatment as an alternative of FSH/IUI. IVM can also be used for fertility preservation in women with cancer who are estrogen receptor positive, or if there is no time or if there is a contraindication to use the hormones, IVM can also be used in luteal phase for fertility preservation and we have performed fertility preservation by IVM/embryo egg freezing in well over 100 patients the last few years. Because of the decline of the fertility and increasing miscarriage rates with maternal age, fertility preservation now is advocated for more patients. Although IVM egg freezing has 20% pregnancy rate/cycle compared with IVF egg freezing rate 50%/cycle, we are now making attempts in animal studies to try to improve the results of IVM egg freezing. Recently, it has been shown that while live birth rate in fresh IVM/ET is lower than fresh IVF/ET cycles, there are comparable live birth rates in frozen embryos IVM/ET versus frozen embryos IVF/ET. We recently reported GnRH agonist trigger in early short stimulation modified natural cycle in IVF/IVM and showed that good results can be obtained with young patients who are treated with this protocol. Most importantly, new centers who start doing IVM can get very good results, for example, in one of our collaborating studies in Turkey; eSET achieved a clinical pregnancy rate/cycle started of 44% in almost for 100 patients after doing IVM <12 months with eSET. In conclusion, IVM simplifies treatments, reduces costs, eliminates OHSS, is successful with women with high AFC; additional hCG increases maturation and number of MII oocytes and may be helpful in an unexplained repeated poor embryo quality or poor responders, and IVM produces up to 50% pregnancy rate in young women and the perinatal outcomes in IVM and IVF are similar. The use of the protocol we have described above has produced a good result for more than a decade, and we have believed that IVM may continue to have a wider place in the use of fertility treatment, but the indications may evolved away from preventing OHSS. Early short stimulation modified natural cycle IVF-IVM may be the first-line approach with less hormones injections, but greater oocytes collected, and up to a 50% pregnancy rate even in new centers.

  Transvaginal ultrasound-guided embryo transfer Top

Seang Lin Tan1,2, Rabea Youcef Khoudja2, Hai Ying Chen3, Justin Tan4, Michael Dahan1,2

1Department of Obstetrics and Gynecology, Division of REI, McGill University, 2OriginElle Fertility Clinic and Women Health Centre, Montreal, 4Department of Obstetrics and Gynecology, University of British Columbia, Canada, 3IVF Department, Northeastern Reproductive Medicine, Vermont, USA, E-mail: kykk888@gmail.com

Initially, embryo transfer (ET) was deemed relatively unimportant to success of in vitro fertilization, and ET was performed in blinded fashion without use of ultrasound (u/s) guidance, but it became apparent that a difficult ET lowers pregnancy rates and that the type of ET catheter, operator skill, site of embryo placement, contamination with mucus of blood, uterine contractions, and difficulty in passing through the cervix affect success rates. u/s-guided ET is typically done with an abdominal probe, transabdominal (TA), and full bladder, and many studies including randomized controlled trials and meta-analysis have shown that TA-u/s-guided ET increases clinical pregnancy and implantation rates compared to a blinded clinical touch method. However, TA-u/s requires abdominal probe held by an assistant, a full bladder which requires scheduling and patient's discomfort and potential cramping during the ET; it is also not well seen by patients and some patients worry about emptying bladder right away after ET. Transvaginal u/s (TV-u/s) significantly improves resolution of uterocervical angle and removes need for full bladder, but it has been suggested that it may be difficult to simultaneously place u/s probe, speculum, and ET catheter. We have performed this procedure as follows. The patient is initially asked to empty her bladder. A Collins or Steiner speculum which has open right side of the blades is then introduced, and the u/s probe is inserted through the speculum to assess the uterine contour and degree of angulation and then removed. For ET, a 3Fr flexible ET catheter (no. 233340; Kitazato Medical Co., Ltd., Tokyo, Japan) is used. The catheter is composed of a semirigid, 20 cm long, 3Fr, precurved (30°) outer sheath with a soft obturator and very thin, hyperflexible, 40 cm long, soft silicone inner catheter. The outer sheath with a small ball-shaped tip is inserted into the cervix until it reaches the internal os. Subsequently, the speculum is gently removed and the TV-u/s probe is reinserted in the vagina while maintaining the already inserted ET catheter in its cervical position. The correct position of the catheter in relation to the internal os is verified on the scan, and a sagittal plane of the uterine body showing the whole endometrial lining is obtained. The soft obturator is removed from the inserted outer sheath after an embryologist loads the embryos into the soft inner catheter. The inner catheter is then threaded into the outer sheath, which is maintained in its position by the physician. Afterward, while holding with one hand the probe and the end of the outer sheath, under continuous TV-u/s control, the readily visible inner catheter was advanced to within a 15-mm distance of the uterine fundus by the physician. Finally, an approximately 0.1 ml media volume is injected into the cavity by the embryologist. The inner catheter is gently removed and examined under the microscope to ensure that the embryos are not left in the catheter. Several studies have shown that higher pregnancy rates with TV-u/s ET compared to clinical touch, and we have reported the first Canadian live birth with this method. We have since treated 47 patients who have failed TA-u/s-guided ETs and have achieved a 53% clinical pregnancy rate. The MD preferred TV-u/s study since no need for full bladder, no need for assistant and abdominal probe and a better view of embryo placement, especially if there is obesity, fibroids, and retroverted uterus. All patients preferred TV-u/s because no discomfort of full bladder; they could see the flash on the u/s screen when the embryos were injected and no concern about emptying bladder right away. In conclusion, TV-u/s-guided ET is preferred by doctors and patients even if no higher live birth rates compared with TA-u/s-guided ET. It is easy to master once a few attempts tried and it reduces cost and personnel.

  In vitro fertilization cycle segmentation: Are we ready for all patients? Top

F Ubaldi, D Cimadomo, L Rienzi

GENERA, Centres for Reproductive Medicine, Valle Giulia Clinic, Rome, Italy, E-mail: ubaldi.fm@gmail.com

The aim of in vitro fertilization (IVF) is to obtain a healthy full-term pregnancy. Possibly, this goal should be reached with the lowest possible complications for the patient. To fulfill this, we need to avoid the ovarian hyperstimulation syndrome, reduce the miscarriage rate, and minimize multiple pregnancy rate as well. Standard care IVF policy has entailed for decades (and still entails in many clinics worldwide) the fresh double/multiple transfer of embryos selected only based on their morphological quality. However, several advances have been implemented in the last decades in IVF: individualized controlled ovarian stimulation, blastocyst culture, trophectoderm biopsy, preimplantation genetic diagnosis for aneuploidy testing, vitrification, and single embryo transfer. We have recently shown that all these improvements in high-quality laboratories do not affect the efficacy of IVF, namely the intrinsic possibilities of a couple to conceive, but significantly increase its efficiency. Freeze-all approach is a pivotal policy to allow the progresses of IVF, especially in terms of embryo selection, meanwhile safeguarding patient's health. Randomized controlled trials and observational studies in the last decades highlighted that frozen embryo transfer might be a more effective and safer alternative to fresh embryo transfer in IVF. The endometrium in a natural cycle is in fact unstimulated and more physiological for embryo's attempt to implant, pregnancy rates are increased, and perinatal outcomes are better. Indeed, the main improvement in terms of safety for the patient is that ovarian hyperstimulation syndrome is minimized through cycle segmentation. The clinical outcomes after a freeze-all approach may vary depending mainly on the ovarian reserve of each specific patient. Nevertheless, no reports up to date have shown the inferiority of this approach with respect to fresh embryo transfer policy in any population of patients, as poor responders for instance. Furthermore, if including the costs of the IVF cycle and the obstetrical and perinatal costs as well, the freeze-all approach has been also reported as a more cost-effective policy with respect to fresh embryo transfer. The limiting factor for a widespread application of the freeze-all policy is the quality of the laboratory, which needs experienced embryologists who adopt a vitrification-based cryopreservation program. However, once such technique is implemented, mainly advantages can derive for the patients with very low or no impact for the embryo.

  Why “more is less and less is more?” Top

Zeev Blumenfeld

IVF Department, Faculty of Medicine, Israel Institute of Technology, Haifa, Israel, E-mail: z_blumenfeld@rambam.health.gov.il

Mild ovarian stimulation protocols for in vitro fertilization (IVF) minimize ovarian hyperstimulation syndrome and multiple gestations without compromising pregnancy rate (PR). What is the putative explanation to the improved outcome of the soft 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 estrogen effect on fetal growth. (3) Improved intrafollicular hormonal milieu. (4) The growth hormone (GH)/insulin-like growth factor (IGF)'s/GH-binding protein (BP). (1) In the natural cycle (NC) 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 folliculogenesis, lasting 4–9 months, only one usually ovulates. Thus, nature eliminates the less than ideal follicles with aneuploidy or other suboptimal genetic, hormonal, or growth factors stimulation, enabling for the continuation of species by the best ova. Indeed, preimplantation genetic screening has demonstrated that milder ovarian stimulation for IVF reduces aneuploidy in human preimplantation embryo. (2) High maternal estrogen in the first trimester correlates with increased risks of low birth weight (LBW) and small for gestational age (SGA). High concentrations of E2 in the late follicular phase of IVF cycles correlate with high E2 levels in the generated gestations at 4 and 8 weeks and significantly correlated with higher rates of SGA and LBW neonates vs. spontaneous pregnancies or those generated by ET of thawed embrya. (3) Is the steroid hormone profile in FF different in naturally matured follicles, (NC-IVF), compared with COS IVF? Indeed, AMH, LH, testosterone, E2, 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 the suboptimal outcome. (4) Normal folliculogenesis is stimulated by follicle-stimulating hormone (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-BP which is increased by E2. It has been suggested that high supraphysiologic levels of E2 (>6000 pM) may increase GH-BP to very high levels which may bio-neutralize GH and diminish the resultant IGF levels, necessary for optimal synergism with FSH.

  Evaluating the endometrial cavity prior to embryo transfer Top

Michael D Scheiber1,2

1IVF Department, Institute for Reproductive Health, 2IVF Department, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA, E-mail: scheibermd@gmail.com

Optimizing the endometrial environment before embryo transfer is a key component to increasing success with assisted reproductive technology. Proper precycle evaluation of the uterine cavity is critical to this optimization. The full range of uterine evaluations and their relative merits will be discussed, and brief videos of corrective procedures will be presented.

  Luteal phase support following intrauterine insemination cycles Top

Peter Kovacs

IVF Center, Kaali Institute, Budapest, Hungary, E-mail: peterkovacs1970@hotmail.com

A menstrual cycle is made up of three distinct phases: proliferative, secretory, and menstrual. The endometrial events of the proliferative phase are primarily guided by the increasing amounts of estradiol secreted by the follicles. Ovulation marks the end of this phase. The luteal phase is primarily guided by progesterone secreted by the corpus luteum. There are characteristic sequential changes that take place after ovulation in preparation for implantation. In stimulated cycles, the hormonal changes differ from the natural cycle. In response to stimulation, multiple follicles grow and significantly higher steroid levels are achieved. Often, premature elevation of progesterone level accompanies stimulation. In addition, multiple corpora lutea form after ovulation. The picture is further complicated by the use of trigger injections (human chorionic gonadotropin [hCG] or gonadotropin-releasing hormone agonist [GnRHa]) to induce timely ovulation. There are clinical situations when the decision to use luteal support seems rather straightforward. These are patients with hypothalamic amenorrhea who benefit from low-dose hCG or combined estradiol-progesterone support of the luteal phase. Those patients who receive GnRHa as the trigger also benefit from luteal support primarily by hCG as GnRHa, due to its short half-life, is unable to provide full support of the corpus luteum. The picture is more controversial in normogonadotropic patients undergoing IUI treatment. In cycles, when clomiphene citrate is used to induce folliculogenesis, most evidence suggests no benefit with luteal support. In gonadotropin-stimulated cycles, on the other hand, there seems to be a benefit with added luteal support. During the presentation, the hormonal changes in a controlled ovarian hyperstimulation-intrauterine insemination (IUI) cycles, the various forms of luteal support and the clinical evidence for any benefit with luteal support in IUI cycles will be discussed.

  Personalized controlled ovarian stimulation to maximize live birth rate in in vitro fertilization Top

F Ubaldi, A Vaiarelli

GENERA, Centres for Reproductive Medicine, Valle Giulia Clinic, Rome, Italy, E-mail: ubaldi.fm@gmail.com

The main goal of any assisted reproductive technique is to obtain a live birth of a healthy child and success in in vitro fertilization (IVF) should be measured by cumulative live birth rate (CLB) per started cycle. The aim of controlled ovarian stimulation is not only to have more eggs, embryos, and embryo transfers but to maximize CLB rates. The prediction of ovarian response is a crucial step in defining to correct protocol to have sufficient number of oocytes. Although the number of oocytes retrieved is poorly correlated to the quality and to the competence of the oocytes, if we have more eggs (>15) we have a greater chance to find the “right oocyte.” Many factors can be used as predictors of ovarian response: age, biochemical parameters (follicle-stimulating hormone [FSH] and anti-Müllerian hormone [AMH]), morphological parameters (antral follicular count) but also clinical conditions such as polycystic ovary syndrome and low body max index. AMH and antral follicle count may be considered good predictors of hyper or hypo responders. According to ovarian reserve, we can individualize three main categories of patients: high responders, normal responders, and poor responders. For each group, we can have different treatment strategies and objectives. For this reason, we can expect different scenarios: (1) in high-responder patients, the main objective is to minimize ovarian hyperstimulation syndrome (OHSS) risk and we should use a gonadotropin-releasing hormone agonists (GnRH) antagonist protocol with minimal FSH stimulation and GnRH agonist trigger; (2) in normal responder patients, we have to maximize success rate and we should use either GnRH agonist or antagonist protocol with correct dose of FSH; (3) in poor responder patients, we must minimize treatment burden with GnRH antagonist protocol, maximal FSH stimulation, and recombinant luteinizing hormone (LH), otherwise we should consider natural IVF or oocyte donation. A combination of GnRH agonist or antagonist with high or mild dose of recombinant FSH with or without recombinant LH should be used to reduce cycle cancellation rates, increase number of oocytes retrieved, produce better quality embryos, and improve outcome. The agonist protocol has advantages such as maximal flexibility and cancellation rate due to premature luteinization <2% but has also disadvantages such as maximal suppression, an increase in side effects, injections, costs, longer treatment, and no possibility in avoiding OHSS. Instead, the GnRH antagonist protocol needs a specific learning curve but is less time-consuming, has less side effects, and gives possibility to use emergency brake with GnRHa triggering to avoid OHSS. Today, strong evidence demonstrates that antagonist protocols with GnRH agonist trigger, embryo vitrification, and frozen embryo transfers represent the optimal strategy in managing hyper-responders to drastically reduce the risks associated with this condition. In conclusion, assessing every single step of the treatment is of utmost importance to maximize the number of oocyte that can be retrieved in each single patient. The correct number of oocyte obtained together with an excellent embryo cryopreservation program must be considered the gold standard to maximize the CLB rates per started cycle, the measure of success in IVF.

  Taking advantage of the natural cycle properties in in vitro fertilization Top

Itai Bar-Hava

IVF Department, E-mail: barhava@gmail.com

Many previous studies have demonstrated higher implantation rates in natural cycle (NC)-in vitro fertilization (IVF) in comparison to controlled ovarian stimulation (COS) IVF cycles. Hyperstimulation of the endometrium and increased progesterone levels toward the end of stimulation during COS cycles are thought to be the causative factors behind this observation. Frozen (vitrified)-thawed cycles result in similar or even better pregnancy rates in comparison with fresh autologous IVF cycles. Furthermore, frozen-thawed embryo transfers are associated with reduced risk for extrauterine pregnancies, antepartum hemorrhage, preterm birth, small for gestational age babies, low birth weight babies and are associated with less perinatal mortality. Thus, it may be concluded that to maximize newborn healthy delivery rate, a two-stage IVF treatment should be considered. Antral follicles count-based hormonal stimulation should be carried out for the purpose of freezing all good embryos followed by transferring them one by one (elective single embryo transfer) in an NC environment.

  References Top

World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Switzerland, Geneva: WHO Press; 2010.  Back to cited text no. 1
Saad Elzanaty, Johan Malm Fertil Steril. 2008;89:1718-22.  Back to cited text no. 2
Wang W, Zhong ZM, Su N, Peng YY, Huang TT. Fertil Steril 2014;20:995-8.  Back to cited text no. 3
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