Is the flexible GnRH antagonist protocol better suited for fresh eSET cycles?

OBJECTIVE: This study was performed to evaluate the efficacy of the flexible GnRH antagonist protocol in comparison with the long GnRH agonist protocol in elective single embryo transfer (eSET) practice. It was conducted in a publicly funded in vitro fertilization program. METHODS: We performed a prospective cohort analysis of data from a private infertility clinic from August 2010 to August 2011. Three hundred fourteen women with normal ovarian reserve and undergoing fresh eSET cycles were included. Sixty-four women underwent follicular stimulation using a flexible GnRH antagonist protocol, and 250 underwent stimulation with a standard long mid-luteal GnRH agonist protocol. RESULTS: Implantation rates (35.9% in the GnRH antagonist group and 29.6% in the GnRH agonist group, P = 0.5) and ongoing pregnancy rates (32.8% in the GnRH antagonist group and 28.8% in the GnRH agonist group, P = 0.5) were equivalent in both groups. The duration of stimulation (9.8 ± 2 days vs. 10.7 ± 1.8 days, P < 0.001) and total FSH dose required (2044 vs. 2775 IU, P < 0.001) were lower in the GnRH antagonist group than in the GnRH agonist group. The number of mature oocytes (6.0 vs. 10.0, P < 0. 001) and number of embryos (5.0 vs. 7.0, P < 0.001) were also lower in GnRH antagonist group. However, the number of embryos cryopreserved was similar in both groups (median 2.0, P = 0.3). CONCLUSION: In women undergoing in vitro fertilization, the flexible GnRH antagonist protocol yields implantation and ongoing pregnancy rates that are similar to the long GnRH agonist protocol, and requires lower doses of gonadotropins and a shorter duration of treatment. The flexible GnRH antagonist protocol appears to be the protocol of choice for an eSET IVF program.

Objectif : La présente étude visait à évaluer l'efficacité d'un protocole flexible ayant recours à des antagonistes de la GnRH, par comparaison avec celle d'un protocole long ayant recours à des agonistes de la GnRH, relativement au transfert sélectif d'un seul embryon (TsSE). L'étude a été menée dans le cadre d'un programme de fécondation in vitro financé par l'État. Méthodes : Nous avons effectué une analyse de cohorte prospective au moyen de données issues d'une clinique de fertilité privée, pour ce qui est de la période d'août 2010 à août 2011. Trois cent quatorze femmes présentant une réserve ovarienne normale et se soumettant à des cycles de TsSE frais ont été admises à l'étude. Un protocole flexible ayant recours à des antagonistes de la GnRH a été utilisé chez 64 femmes, aux fins de la stimulation folliculaire, tandis qu'un protocole long en phase lutéale standard ayant recours à des agonistes de la GnRH a été utilisé chez 250 autres femmes. Résultats : Les taux d'implantation (35,9 % au sein du groupe « antagonistes de la GnRH ¼ et 29,6 % au sein du groupe « agonistes de la GnRH ¼, P = 0,5) et les taux de grossesse en cours (32,8 % au sein du groupe « antagonistes de la GnRH ¼ et 28,8 % au sein du groupe « agonistes de la GnRH ¼, P = 0,5) étaient équivalents dans les deux groupes. La durée de la stimulation (9,8 jours ± 2 jours vs 10,7 jours ± 1,8 jour, P < 0,001) et la dose totale de FSH requise (2 044 vs 2 775 UI, P < 0,001) étaient moins élevées au sein du groupe « antagonistes de la GnRH ¼, par comparaison avec le groupe « agonistes de la GnRH ¼. Le nombre d'ovocytes matures (6,0 vs 10,0, P < 0,001) et le nombre d'embryons (5,0 vs 7,0, P < 0,001) étaient également moins élevés au sein du groupe « antagonistes de la GnRH ¼. Cependant, le nombre d'embryons cryoconservés était similaire dans les deux groupes (médiane : 2,0, P = 0,3). Conclusion : Chez les femmes qui font appel à la fécondation in vitro, le protocole flexible ayant recours à des antagonistes de la GnRH donne des taux d'implantation et de grossesse en cours similaires à ceux que permet le protocole long standard ayant recours à des agonistes de la GnRH, tout en nécessitant des doses plus faibles de gonadotropines et un traitement de plus courte durée. Le protocole flexible ayant recours à des antagonistes de la GnRH semble être le protocole à privilégier dans le cadre d'un programme de FIV utilisant le TsSE.

Rescue in vitro fertilization using a GnRH antagonist in hyper-responders from gonadotropin intrauterine insemination (IUI) cycles.

OBJECTIVE: To evaluate the outcomes in the conversion of high-response gonadotropin intrauterine insemination (IUI) cycles to "rescue" in vitro fertilization (IVF) using a Gonadotropin-Releasing Hormone (GnRH) antagonist, with regards to implantation rates, pregnancy rates, cost, and ovarian hyperstimulation syndrome (OHSS) as compared to matched, hyper-responder, IVF controls. METHODS: This prospective cohort study was conducted between January 2007 and December 2009 at our institution. In order to decrease high-order multiple pregnancy, minimize the incidence of OHSS, and avoid cycle cancellation, high-response stimulated-IUI patients opted to convert to "rescue" IVF using the GnRH antagonist cetrorelix acetate. We then compared their clinical outcomes with matched patients from high-response IVF cycles of the standard long mid-luteal GnRH agonist protocol (14 or more collected oocytes). Only cases of conventional IVF without intra-cytoplasmic sperm injection (ICSI) were included in the control group. RESULTS: Out of 184 patients undergoing stimulated-IUI cycles with gonadotropins, 87 patients developed a hyper-response, and 20 opted to convert to "rescue" IVF. These patients were compared with 157 matched, hyper responder IVF controls from our registry. The implantation rate was 25.6 % in the "rescue" IVF group and 20.7 % in the control IVF group (p < 0.0047). The ongoing clinical pregnancy rate per embryo transfer was 45.0 % and 33.6 % in the "rescue" IVF and the control IVF groups, respectively (p < 0.0001). The mean duration of stimulation was comparable between cohorts (10.0 vs.10.4 days, p = 0.6324). The mean dose of gonadotropin used per cycle was higher in the control group, 2664 international units (IU) of follicle stimulation hormone (FSH) compared to 1450 IU of FSH in the "rescue" IVF group (p < 0.0001). The incidence of severe OHSS is also higher in the control group, 5.1 % versus no cases in the "rescue" IVF group (p < 0.0001). CONCLUSION: Our study demonstrates that conversion of high-response gonadotropin-IUI cycles to "rescue" IVF using a GnRH antagonist is a cost-effective strategy that produces better results than regular IVF with relatively minimal morbidity, and shorter duration to achieve pregnancy. Implantation and ongoing clinical pregnancy rates tend to be higher than those from hyper-responder regular IVF patients.

Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome.

OBJECTIVE: To determine which first-line medication is more effective in polycystic ovary syndrome (PCOS) patients for ovulation induction and pregnancy achievement and to verify whether any patient characteristic is associated with a better response to therapy. DESIGN: Observational comparative study. SETTING: Fertility clinic. PATIENT(S): One hundred fifty-four infertile women with oligomenorrhea and hyperandrogenism. INTERVENTION(S): Group 1 (56 patients) received clomiphene citrate (CC) 50 mg from days 5-9 of the cycle. Group 2 (57 patients) received 500 mg of metformin 3 times a day. Group 3 (41 patients) received both medications. MAIN OUTCOME MEASURE(S): Ovulation and pregnancy. RESULT(S): Patients receiving metformin alone had an increased ovulation rate compared with those receiving CC alone (75.4% vs. 50%). Patients on metformin had similar ovulation rates compared with those in the combination group (75.4% vs. 63.4%). Pregnancy rates were equivalent in the 3 groups. Response to metformin was independent of body weight and dose. Finally, nonsmoking predicted better ovulatory response overall as well as lower fasting glucose for CC and lower androgens for metformin. CONCLUSION(S): Metformin is better for ovulation induction than CC alone and equivalent for pregnancy achievement. We suggest that metformin can be used first for ovulation induction in patients with PCOS regardless of their weight and insulin levels because of its efficacy and known safety profile.