Use of a gonadotropin-releasing hormone antagonist for endometrial maturation and synchronization in an ovum recipient

OBJECTIVE: To report the novel use of hMG and the GnRH antagonist for endometrial preparation and synchronization in a woman participating in an ovum donation program who was resistant to endometrial preparation with estrogen replacement. DESIGN: Case report. SETTING: Tertiary fertility center. PATIENT(S): The patient had inadequate endometrial maturation, as determined by pelvic ultrasound (thickness of <5 mm), after estrogen replacement. Ovarian hyperstimulation with hMG and a GnRH antagonist resulted in an endometrial thickness of 7.5 mm. Synchronization with a ovum donor resulted in a delivered twin gestation. INTERVENTION(S): : Late follicular transvaginal ultrasound. MAIN OUTCOME MEASURE(S): Appropriate endometrial maturation and pregnancy. RESULT(S): Appropriate endometrial maturation. CONCLUSION(S): For women with inadequate endometrial maturation with simple estrogen replacement, ovarian hyperstimulation with hMG and a GnRH antagonist can yield appropriate endometrial maturation for pregnancy through ovum donation.     

Premenstrual administration of gonadotropin-releasing hormone antagonist coordinates early antral follicle sizes and sets up the basis for an innovative concept of controlled ovarian hyperstimulation

OBJECTIVE: To investigate whether premenstrual administration of a GnRH antagonist coordinates early antral follicle sizes during the subsequent follicular phase. DESIGN: Prospective, longitudinal study. SETTING: University Hospital in France PATIENT(S): Twenty-five women, 50 cycles. INTERVENTION(S): On cycle day 2 (control/day 2), women underwent measurements of early antral follicles by ultrasound and serum FSH and ovarian hormones. On day 25, they received a single cetrorelix acetate administration, 3 mg. On the subsequent day 2 (premenstrual GnRH antagonist/day 2), participants were re-evaluated as on control/day 2. MAIN OUTCOME MEASURE(S): Magnitude of follicular size discrepancies. RESULT(S): Follicular diameters (4.1 +/- 0.9 vs. 5.5 +/- 1.0 mm) and follicle-to-follicle size differences decreased on premenstrual GnRH antagonist/day 2 as compared with control/day 2. Consistently, FSH (4.5 +/- 1.9 vs. 6.7 +/- 2.4 mIU/mL), E(2) (23 +/- 13 vs. 46 +/- 26 pg/mL), and inhibin B (52 +/- 30 vs. 76 +/- 33 pg/mL) were lower on GnRH antagonist/day 2 than on control/day 2. CONCLUSION(S): Premenstrual GnRH antagonist administration reduces diameters and size disparities of early antral follicles on day 2, likely through the prevention of luteal FSH elevation and early follicular development. This simple, original approach may be used to coordinate multifollicular development in controlled ovarian hyperstimulation.     

Luteolysis induced by a gonadotropin-releasing hormone agonist is the key to prevention of ovarian hyperstimulation syndrome

OBJECTIVE: To review the available knowledge on the use of GnRH agonist for ovulation triggering as a means to prevent ovarian hyperstimulation syndrome (OHSS). DESIGN(S): Review of pertinent English language studies published over the past 15 years. RESULT(S): The available literature suggests that while GnRH agonist effectively induces final oocyte maturation and ovulation, it also completely and reliably prevents clinically significant OHSS. The mechanism of action in the context of OHSS prevention involves complete, quick, and irreversible luteolysis CONCLUSION(S): Controlled ovarian stimulation protocols based on GnRH antagonist to prevent premature LH rise and GnRH agonist for ovulation triggering provide a safe and OHSS-free clinical environment. Adequate luteal support compensates for luteolysis and assures good clinical outcome. The fertility community is urged to adopt these protocols. This will make OHSS a disease of the past.     

Luteinizing hormone supplementation increases pregnancy rates in gonadotropin-releasing hormone antagonist donor cycles

OBJECTIVE: To determine whether LH supplementation improved pregnancy and implantation rates in GnRH antagonist donor cycles. DESIGN: Donors were randomly assigned to a protocol using GnRH antagonist (GnRH-a) alone or GnRH-a + recombinant LH. Analysis of variance, Student's t-test and Fisher's exact test were used where appropriate. SETTING: Private clinical setting. PATIENT(S): Young voluntary donors with antagonist (n = 20) and antagonist + LH (n = 22). Fifty-five patients received oocytes. INTERVENTION(S): Donors received the GnRH-a (Cetrorelix, 0.25 mg/day) alone or in combination with recombinant LH (75 IU/day). Ovulation induction was carried out with recombinant FSH in a step-down protocol. The endometrial tissue of recipient patients was prepared with oral E(2) and P. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates in a donor program. RESULT(S): A significant increase in MII oocyte (80% vs. 71%), fertilization rates (83% vs. 71%), G1 embryos (17% vs. 3%), and implantation rates (35% vs. 15%), were found in recipients whose embryos originated from donors receiving GnRH-a + recombinant LH as compared to donors receiving GnRH-a alone. Estradiol levels, pregnancy/transfer and clinical pregnancies were lower (not significant) in donors treated with the GnRH-a alone vs. those receiving the recombinant LH-supplemented GnRH-a. CONCLUSION(S): The LH supplementation improved the possibilities of gestation for recipients whose embryos originated from GnRH-a-treated donors.     

Comparison of cryopreservation outcome with gonadotropin-releasing hormone agonists or antagonists in the collecting cycle

OBJECTIVE: To compare the pregnancy rates of frozen-thawed 2-pronucleate (2PN) oocytes obtained either in a long protocol or in an antagonist protocol and ovarian stimulation with either human menopausal gonadotropin (hMG) or recombinant follicular stimulating hormone (recFSH). DESIGN: Retrospective data analysis. SETTING: Academic infertility center. PATIENT(S): Three hundred forty-two infertile couples who underwent a transfer of cryopreserved 2PN oocytes. INTERVENTION(S): hMG (n = 194) or recFSH (n = 92) in a long protocol or hMG (n = 16) or recFSH (n = 40) stimulation under pituitary suppression with the GnRH antagonist Cetrotide was used. The 2PN oocytes were transferred after endometrial preparation using E(2) valerate and vaginal progesterone (Crinone 8% vaginal gel). MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and abortion rates. RESULT(S): Implantation rates in the freeze-thaw cycles were 5.6% (hMG) and 3.8% (recFSH) with 2PN oocytes from the long protocol and 7% from the antagonist cycles, irrespective of whether hMG or recFSH was used. Pregnancy rates were similar independent of whether they resulted from the long-protocol cycles with hMG (15.4%) and recFSH (13.1%) or from the antagonist protocol cycles with hMG (25.0%) and recFSH (17.5%). CONCLUSION(S): The potential to implant is independent of the gonadotropin-releasing hormone analogue and gonadotropin chosen for the collection cycle when previously cryopreserved 2PN oocytes were replaced after thawing in the cleavage stage.     

Gonadotropin releasing hormone antagonist use in controlled ovarian stimulation and intrauterine insemination cycles in women with polycystic ovary syndrome

Objective

To evaluate the effect of the GnRH antagonist on gonadotropin ovulation induction in women with PCOS.

Dopamine agonists in prevention of ovarian hyperstimulation syndrome

The aim of this review is to analyze the efficacy of different dopamine agonists in the prevention of ovarian hyperstimulation syndrome (OHSS). Cabergoline, quinagolide and bromocriptine are the most common dopamine agonists used. There are wide clinical variations among the trials in the starting time (from the day of human chorionic gonadotrophin (hCG) to the day following oocyte retrieval); the duration of the treatment (4–21 days), the dose of cabergoline (0.5?mg or 0.25?mg orally) and in the regimens used. At present, the best known effective regimen is 0.5?mg of cabergoline for 8 days or rectal bromocriptine at a daily dose of 2.5?mg for 16 days. Dopamine agonists have shown significant evidences of their efficacy in the prevention of moderate and early-onset OHSS (9.41%), compared with a placebo (21.45%), which cannot be confirmed for the treatment of late OHSS. It would be advisable to start with the treatment on the day of hCG injection or preferably a few hours earlier. The use of dopamine agonists should be indicated in patients at high risk of OHSS, as well as in patients with a history of previous OHSS even without evident signs of the syndrome.     

黄体期促性腺激素释放激素拮抗剂在防治卵巢过度刺激综合征的应用进展

卵巢过度刺激综合征(ovarian hyperstimulation syndrome,OHSS)是辅助生殖技术(ART)相关的并发症,是以卵巢体积增大、毛细血管通透性增加、体液外渗为特征的一个系统性综合征。目前已知许多可预测OHSS发生的高危因素并给予预防措施,但因其病因尚未明确,临床表现形式多样,给临床干预和治疗带来了不少困难。近年来有文献报道,ART取卵后黄体期应用促性腺激素释放激素拮抗剂(gonadotropin-releasing hormone antagonist,Gn RH-A)能预防和治疗OHSS。本文将综述黄体期应用G n R H-A在防治O H S S的作用。     

改良GnRH-a长方案在控制性促排卵中的应用

目的探讨改良GnRH—a/FSH/hMG联合长方案在控制性促排卵中的应用以及国产阿拉瑞林在此方案中的使用。方法以回顾性分析的方法对174例改良GnRH-a长方案和48例超短方案控制性促排卵的资料进行回顾性分析。结果 改良GnRH—a/FSH/hMG联合长方案在FSH/hMG用药天数、用药量、取卵数、移植数、冻存胚胎数、hCG丑内膜厚度、临床妊娠率、种植率、流产率、OHSS发生率等方面与短方案组相比差异均无显著性(P>0.05),其中流产率明显低于超短方案组。结论改良国产阿拉瑞林/FSH/hMG联合长方案是一种简单、经济、有效的控制性促排卵方案,值得在IVF—ET周期中推广。