A. Diluigi

Meiotic Arrest in Human Oocytes Is Maintained by a Gs Signaling Pathway

Abstract In mammalian oocytes, the maintenance of meiotic prophase I arrest prior to the surge of LH that stimulates meiotic maturation depends on a high level of cAMP within the oocyte. In mouse and rat, the cAMP is generated in the oocyte, and this requires the activity of a constitutively active, Gs–linked receptor, GPR3 or GPR12, respectively. To examine if human oocyte meiotic arrest depends on a similar pathway, we used RT-PCR and Western blotting to look at whether human oocytes express the same components for maintaining arrest as rodent oocytes. RNA encoding GPR3, but not GPR12, was expressed. RNA encoding adenylate cyclase type 3, which is the major adenylate cyclase required for maintaining meiotic arrest in the mouse oocyte, was also expressed, as was Gαs protein. To determine if this pathway is functional in the human oocyte, we examined the effect of injecting a function-blocking antibody against Gαs on meiotic resumption. This antibody stimulated meiotic resumption of human oocytes that were maintained at the prophase I stage using a phosphodiesterase inhibitor. These results demonstrate that human oocytes maintain meiotic arrest prior to the LH surge using a signaling pathway similar to that of rodent oocytes.

Effects of gonadotropin-releasing hormone agonists and antagonists on luteal function.

Purpose of review This review addresses the effects of gonadotropin-releasing hormone agonists and antagonists on various aspects of the luteal phase. Recent findings Recent studies have shown that use of both gonadotropin-releasing hormone agonists and antagonists during in-vitro fertilization cycles leads to alterations in the hormonal profiles of the luteal phase as well as changes in endometrial histology. Gonadotropin-releasing hormone agonists are effective in triggering final oocyte maturation and reducing the incidence of ovarian hyperstimulation syndrome. Ongoing pregnancy rates are excellent after gonadotropin-releasing hormone agonist trigger when luteal phase and early pregnancy supplementation with estradiol and progesterone is provided. Gonadotropin-releasing hormone agonists have recently been used for luteal phase support in in-vitro fertilization cycles. Summary Although gonadotropin-releasing hormone agonists and antagonists are clinically useful, they may have adverse effects on luteal function. Luteal phase supplementation significantly improves clinical outcomes in in-vitro fertilization cycles because it may correct some of these detrimental effects. Use of gonadotropin-releasing hormone agonist to induce oocyte maturation is beneficial to patients who are at increased risk for ovarian hyperstimulation syndrome. The key factor in achieving favorable ongoing pregnancy rates with use of gonadotropin-releasing hormone agonist to induce oocyte maturation appears to be adequate luteal phase support.

Gonadotropin-releasing hormone agonist to induce final oocyte maturation prevents the development of ovarian hyperstimulation syndrome in high-risk patients and leads to improved clinical outcomes compared with coasting

Ninety-four women undergoing IVF with peak E2 level>4000 pg/mL received leuprolide acetate (LA) trigger (LA trigger group) or had gonadotropins withheld for one or more days (coasting group) followed by hCG trigger, unless cycle cancellation occurred. There were no cases of ovarian hyperstimulation syndrome in either group, and the LA trigger group had significantly more oocytes retrieved (26.9+/-9.5 vs. 17.7+/-9.3) P<0.001, more normally fertilized oocytes (15.0+/-7.8 vs. 10.3+/-6.3) P=0.01, and higher clinical and ongoing pregnancy rates than the coasting group (52.5% vs. 27.2%; 49.2% vs. 24.2%, P=0.02 for both comparisons, respectively).

Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes

OBJECTIVE To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. DESIGN Retrospective analysis. SETTING University-based IVF center. PATIENT(S) Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. MAIN OUTCOME MEASURE(S) Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. RESULT(S) The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. CONCLUSION(S) This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups.

Ruptured ectopic pregnancy with contralateral adnexal torsion after spontaneous conception

OBJECTIVE To describe a case of ruptured ectopic pregnancy and contralateral adnexal torsion after spontaneous conception. DESIGN Case report. SETTING Tertiary university medical center. PATIENT(S) A 23-year-old multiparous female with severe bilateral pelvic pain and a positive pregnancy test. INTERVENTION(S) Operative laparoscopy with detorsion of left adnexa, drainage of left ovarian hemorrhagic corpus luteum cyst, right salpingectomy, and dilation and curettage. MAIN OUTCOME MEASURE(S) Laparoscopy revealed a 5 cm hemorrhagic corpus luteum cyst of the left ovary, torsion of the left ovary and fallopian tube, and a ruptured right ampullary ectopic pregnancy. RESULT(S) Normal perfusion of left ovary and fallopian tube after detorsion, resolution of left ovarian hemorrhagic corpus luteum cyst, patent left fallopian tube with chromopertubation, and successful removal of ectopic pregnancy. CONCLUSION(S) This is a unique case of adnexal torsion and contralateral ectopic pregnancy occurring after spontaneous conception.

Ovulation rate and cycle characteristics in a subsequent clomiphene citrate cycle after stair-step protocol

OBJECTIVE To determine the ovulation rate after ovulation induction with clomiphene citrate (CC) in women who had previously been ovulatory after a stair-step (CC-SS) ovulation induction. DESIGN Retrospective cohort. SETTING University-based tertiary fertility center. PATIENT(S) 61 anovulatory patients <40 years of age with polycystic ovary syndrome who underwent ovulation induction with a CC-SS protocol and a subsequent CC cycle. INTERVENTION(S) Ovulation induction with CC. MAIN OUTCOME MEASURE(S) Ovulation rates and cycle characteristics. RESULT(S) Of 61 patients who underwent a subsequent CC cycle, 15 (25%) failed to ovulate at the previously ovulatory dose. Of those 15 patients, 13 (86.7%) ovulated after an increase in dose. The total number of follicles ≥15 mm (2.8 ± 1.2 vs. 1.6 ± 0.7) and peak estradiol (E2) levels (604 ± 272 pg/mL vs. 447 ± 218 pg/mL) were statistically significantly higher in the CC-SS cycle compared with the subsequent CC cycle, respectively. The endometrial lining was statistically significantly thinner in the CC-SS than the CC cycle (7.8 ± 1.8 vs. 9.2 ± 2.7, respectively). CONCLUSION(S) The majority of patients who ovulate after a CC-SS protocol will ovulate after taking the previously ovulatory CC dose in a subsequent cycle. Those who do not ovulate will likely ovulate with a further increase in CC dose.

The dual trigger study: Rationale and study design of a prospective double-blind randomized clinical trial comparing pregnancy rates after co-administration of low dose hCG at the time of GnRH agonist trigger or 35 h later for the prevention of OHSS

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of controlled ovarian stimulation. The use of gonadotropin releasing hormone (GnRH) agonist for the trigger of oocyte maturation is effective in the prevention of OHSS although it may result in a lower pregnancy rate. The use of adjuvant low dose human chorionic gonadotropin (hCG) at the time of trigger or at the time of oocyte retrieval may improve pregnancy rates. The goal of this dual trigger study is to evaluate the safety and efficacy of the use of low dose hCG administered at the time of GnRH agonist trigger or 35 h later as well as the potential impact on pregnancy rates. The population will consist of 82 women undergoing IVF treatment who are at risk of developing OHSS. This study will be a single center prospective randomized double-blind placebo controlled trial. The randomization schedule will be administered by the Investigational Drug Services of the University. After controlled ovarian stimulation, induction of oocyte maturation will be achieved using a GnRH agonist and patients will be randomized to receive either low dose hCG 1000 IU at the time of trigger and placebo at oocyte retrieval (Study group) or placebo at the time of trigger and hCG 1500 IU at the time of oocyte retrieval (Control group). The main outcomes will be live birth rates and incidence of OHSS. Two ancillary studies will include a quality of life survey and serum assessment of independent corpus luteum function.

Effects of Gonadotropin-Releasing Hormone Agonists And Antagonists on Luteal Function

Purpose of review This review addresses the effects of gonadotropinreleasing hormone agonists and antagonists on various aspects of the luteal phase. Recent findings Recent studies have shown that use of both gonadotropinreleasing hormone agonists and antagonists during in-vitro fertilization cycles leads to alterations in the hormonal profiles of the luteal phase as well as changes in endometrial histology. Gonadotropin-releasing hormone agonists are effective in triggering final oocyte maturation and reducing the incidence of ovarian hyperstimulation syndrome. Ongoing pregnancy rates are excellent after gonadotropin-releasing hormone agonist trigger when luteal phase and early pregnancy supplementation with estradiol and progesterone is provided. Gonadotropinreleasing hormone agonists have recently been used for luteal phase support in in-vitro fertilization cycles. Summary Although gonadotropin-releasing hormone agonists and antagonists are clinically useful, they may have adverse effects on luteal function. Luteal phase supplementation significantly improves clinical outcomes in in-vitro fertilization cycles because it may correct some of these detrimental effects. Use of gonadotropin-releasing hormone agonist to induce oocyte maturation is beneficial to patients who are at increased risk for ovarian hyperstimulation syndrome. The key factor in achieving favorable ongoing pregnancy rates with use of gonadotropin-releasing hormone agonist to induce oocyte maturation appears to be adequate luteal phase support.