Inadvertent premature human chorionic gonadotropin administration does not prevent folliculogenesis and in vitro fertilization

Zeev Blumenfeld

doi:10.4103/2348-2907.164849

CASE REPORT

Year : 2015 | Volume : 2 | Issue : 2 | Page : 64-66

Inadvertent premature human chorionic gonadotropin administration does not prevent folliculogenesis and in vitro fertilization

Zeev Blumenfeld
Department of Obstetrics and Gynecology, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel

Date of Web Publication

9-Sep-2015

Correspondence Address:
Zeev Blumenfeld
Reproductive Endocrinology, Dept. OB/GYN, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 8 Haaliyah St, Haifa, Israel. 31096
Israel

Source of Support: Nil., Conflict of Interest: There are no conflicts of interest.

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DOI: 10.4103/2348-2907.164849

Abstract

A 41.9-year-old patient, G 10101, was referred for fertility preservation 2 weeks before chemotherapy, due to metastatic liver malignancy. Her past history was positive for laparoscopic sigmoidectomy, 5 years ago due to stage I colon carcinoma. She has undergone a normal vaginal delivery in her previous marriage, 15 years ago and a septic abortion, 2 days after amniocentesis, a year ago, in her current marriage. Despite high follicle stimulating hormone (FSH), she started ovarian stimulation with high dose recombinant gonadotropins and gonadotrophin-releasing hormone antagonist, on the 6^th day of her cycle, in the presence of two antral follicles. By mistake, she injected 650 µg of human chorionic gonadotropin (hCG), in addition to 450 units FSH/luteinizing hormone (Pergoveris, Merck Serono) on the 1^st day of stimulation. The controlled ovarian stimulation continued and on the 18^th cycle day, 650 µg of hCG was administered and 35.5 h afterward, two metaphase II ova were retrieved by vaginal follicular aspiration. The ova have undergone intracytoplasmic sperm injection and fertilization was documented after 20 h, and two embryos were cryopreserved on the 2^nd day. This unusual case suggests that premature exposure to supraphysiological concentrations of hCG and progesterone, may not interfere with normal folliculogenesis, oocyte maturation, and in vitro fertilization.

Keywords: Controlled ovarian stimulation, fertility preservation, in vitro fertilization, premature human chorionic gonadotropin, random start ovarian stimulation

How to cite this article:
Blumenfeld Z. Inadvertent premature human chorionic gonadotropin administration does not prevent folliculogenesis and in vitro fertilization. IVF Lite 2015;2:64-6

How to cite this URL:
Blumenfeld Z. Inadvertent premature human chorionic gonadotropin administration does not prevent folliculogenesis and in vitro fertilization. IVF Lite [serial online] 2015 [cited 2023 Sep 25];2:64-6. Available from: http://www.ivflite.org/text.asp?2015/2/2/64/164849

Introduction

The increase in cancer incidence in the young age, and the significant increase in the long-term survival have brought about a ubiquitous interest in the attempts to preserve fertility in young patients exposed to gonadotoxic chemo- and radiotherapy.^{[1],[2],[3],[4],[5]} Indeed, malignancy is estimated to occur in 1:49 women under the age of 40 in the US.^[1],[2] It has been previously estimated that at present, one in every 250–715 people in the adult population will be a cancer survivor.^[1],[2] Therefore, the late effects of cancer treatment have recently gained a worldwide interest not only among reproductive endocrinologists but also among hematologists, oncologists, gynecologists, endocrinologists, rheumatologists, family physicians, and all health care providers,^{[1],[2],[3],[4],[5]} and the protection against iatrogenic infertility caused by chemotherapy assumes a high priority.

Several options have been put forward for preserving female fertility: Ovarian transposition, cryopreservation of embryos, unfertilized metaphase II (M-II) oocytes, and ovarian tissue, and administration of gonadotropin-releasing hormone (GnRH)-agonistic analogs in an attempt to decrease the gonadotoxic effects of chemotherapy by simulating a prepubertal hormonal milieu.^{[1],[2],[3],[4],[5]} Indeed, in the last decade, a dramatic increase in the number of publications regarding fertility preservation has been experienced. Unfortunately, none of the suggested methods is ideal, and none guarantees future fertility in survivors. In vitro fertilization (IVF) and embryo cryopreservation, the only noninvestigational, clinically established method, used to necessitate postponing chemotherapy for at least 10–14 days, and is frequently not applicable to the very young patient without a partner. The following case report, similar to other recent publications,^[6],[7] suggests that premature exposure to supraphysiological concentrations of human chorionic gonadotropin (hCG) and progesterone, may not interfere with normal folliculogenesis, oocyte maturation, and IVF.

Case Report

A 41.9-year-old patient, gravida 2, para 1, abortion 1, was referred for fertility preservation 2 weeks before chemotherapy, due to metastatic liver malignancy. Her past history was positive for laparoscopic sigmoidectomy, 5 years ago due to stage I colon carcinoma. She did not receive any previous chemo- or radio-therapy. In her infancy, she has undergone surgery due to congenital dislocation of the hip. She has undergone a normal vaginal delivery, in her previous marriage, 15 years ago, and a septic abortion in the 19^th week of a spontaneous pregnancy, 2 days after amniocentesis, in another hospital, a year ago, in her current marriage. Her menstrual periods were irregular, ranging between 17 and 40 days and the last menses started 6 days before referral. The follicle stimulating hormone (FSH) = 20.9 U/L, estradiol 80 picomolar, progesterone 2.5 nanomolar, CA 19-9 = 618.2 U/mL (nuclear receptor [NR] <39 U/mL), carcinoembryonic antigen = 39.1 ng/mL (NR < 5.5 ng/mL), lactate dehydrogenase = 878 U/L (NR = 230–480 U/L), gamma glutamyl transferase = 105 U/L [NR = 5–38 U/L], and alkaline phosphatase 178 U/L [NR = 30–120 U/L]. The imaging methods and positron emission tomography/computed tomography were compatible with metastatic space occupying lesions in the right lobe of the liver and retroperitoneal lymph nodes. Due to the high FSH levels, she was advised against GnRH agonist co-treatment and ovarian tissue cryopreservation. However, despite the high FSH, due to the presence of two antral follicles, she insisted on an attempt to try controlled ovarian stimulation (COS) for IVF and cryopreservation of embryo.

Despite high FSH, she started ovarian stimulation with high dose recombinant gonadotropins and GnRH antagonist, on the 6^th day of her cycle, in the presence of two antral follicles. By mistake, she injected 650 µg of hCG, in addition to 450 units FSH/luteinizing hormone (LH) (Pergoveris, Merck Serono) on the 1^st day of stimulation. The COS continued and on the 18^th cycle day, 650 µg of hCG was administered and 35.5 h afterward, two M-II ova were retrieved by transvaginal follicular aspiration. The ova have undergone intracytoplasmic sperm injection and fertilization was documented after 20 h, and two embryos were cryopreserved on the 2^nd day. This unusual case suggests that premature exposure to supraphysiological concentrations of hCG and progesterone, may not interfere with normal folliculogenesis, oocyte maturation, and IVF.

Conclusions

The implication of the presented case report is in keeping with previous reports,^[6],[7] whereby it is possible to random start COS on any day of the menstrual cycle, disregarding LH and progesterone levels, once the retrieved ova, and/or generated embryos are cryopreserved and do not undergo embryo transfer in the fresh cycle.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Blumenfeld Z, Evron A. Preserving fertility when choosing chemotherapy regimens – The role of gonadotropin-releasing hormone agonists. Expert Opin Pharmacother 2015;16:1009-20.
2.	Blumenfeld Z, Katz G, Evron A. 'An ounce of prevention is worth a pound of cure': The case for and against GnRH-agonist for fertility preservation. Ann Oncol 2014;25:1719-28.
3.	The Practice Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in cancer patients. Fertil Steril 2005;83:1622-8.
4.	Practice Committees of American Society for Reproductive Medicine; Society for Assisted Reproductive Technology. Mature oocyte cryopreservation: A guideline. Fertil Steril 2013;99:37-43.
5.	McLaren JF, Bates GW. Fertility preservation in women of reproductive age with cancer. Am J Obstet Gynecol 2012;207:455-62.
6.	Cakmak H, Rosen MP. Random-start ovarian stimulation in patients with cancer. Curr Opin Obstet Gynecol 2015;27:215-21.
7.	Kim JH, Kim SK, Lee HJ, Lee JR, Jee BC, Suh CS, et al. Efficacy of random-start controlled ovarian stimulation in cancer patients. J Korean Med Sci 2015;30:290-5.

Authors

Associate Professor at the faculty of medicine of the Technion, Israel Institute of Technology, and director of Reproductive Endocrinology and Infertility at RAMBAM Health Care Campus, Haifa, and Head of Women Health Ctr, and chief gynecologist at Northern Meuhedeth Health Care, Israel. Main research & interest areas: Fertility preservation despite chemotherapy, ART/IVF, Premature Ovarian Failure, PCOS, Hypophysiotropic factors, AMH, Inhibin, Activin.