Controlled Ovarian Stimulation Using Medroxyprogesterone Acetate and hMG in Patients With Polycystic Ovary Syndrome Treated for IVF

Abstract

Ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation is a current challenge for patients with polycystic ovarian syndrome (PCOS). Our previous studies indicated that progestin can prevent premature luteinizing hormone (LH) surge or moderate/severe OHSS in the general subfertile population, both in the follicular-phase and luteal-phase ovarian stimulation but it is unclear if this is true for patients with PCOS.The aim of the article was to analyze cycle characteristics and endocrinological profiles using human menopausal gonadotropin (hMG) in combination with medroxyprogesterone acetate (MPA) for PCOS patients who are undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments and investigate the subsequently pregnancy outcomes of frozen embryo transfer (FET).In the randomized prospective controlled study, 120 PCOS patients undergoing IVF/ICSI were recruited and randomly classified into 2 groups according to the ovarian stimulation protocols: hMG and MPA (group A, n = 60) or short protocol (group B, n = 60).In the study group, hMG (150–225IU) and MPA (10 mg/d) were administered simultaneously beginning on cycle day 3. Ovulation was cotriggered by a gonadotropinreleasing hormone (GnRH) agonist (0.1 mg) and hCG (1000IU) when dominant follicles matured. A short protocol was used as a control.The primary end-point was the ongoing pregnancy rate per transfer and incidence of OHSS.Doses of hMG administrated in group A are significantly higher than those in the controls. LH suppression persisted during ovarian stimulation and no incidence of premature LH surge was seen in both groups. The fertilization rate and the ongoing pregnant rate in the study group were higher than that in the control. The number of oocytes retrieved, mature oocytes, clinical pregnancy rates per transfer, implantation rates, and cumulative pregnancy rates per patient were comparable between the 2 groups. The incidence of OHSS was low between the 2 groups, with no significant difference.The study showed that MPA has the advantages of an oral administration route, easy access, more control over LH levels. A possible reduction in the incidence of moderate or severe OHSS with the MPA protocol should be viewed with caution as the data is small. Large randomized trials with adequate sample size remain necessary.

Progestin‐primed ovarian stimulation with or without clomiphene citrate supplementation in normal ovulatory women undergoing in vitro fertilization/intracytoplasmic sperm injection: A prospective randomized controlled trial

“…With the development of advanced cryopreservation techniques and “freeze‐all” strategies, which enable freezing of entire cohorts of embryos, we can consider more ovarian stimulation protocols without potential detrimental effects on endometrial receptivity or the risk of OHSS . Progesterone (P) is an effective alternative to GnRH analogues for suppression of a premature LH surge during controlled ovarian stimulation (COS) for in vitro fertilization (IVF) cycles based on the freeze‐all strategy . The COS with medroxyprogesterone acetate (MPA) method is referred to as the progestin‐primed ovarian stimulation (PPOS) protocol .…”

<p>Comparison Between PPOS and GnRHa-Long Protocol in Clinical Outcome with the First IVF/ICSI Cycle: A Randomized Clinical Trial</p>

“…These findings are in agreement with those of previous studies that compared PPOS with the short protocol. 6,12,13 The results suggest that using progesterone during ovarian stimulation may have a weaker ability to suppress the HPO axis than GnRH agonist. One possible reason for this phenomenon is related to the different mechanisms to suppress the LH surge of the two protocols during COH.…”

“…15 Another highlight of this study is that none of the patients went through moderate and severe OHSS in the study group, which showed the same result with our previous studies. 6,12,13 However, there were three women in the GnRHa long group suffered moderate and severe OHSS. In this trial, PPOS was a protocol in combination with "freeze-all strategy", and we cancelled the fresh embryo transfer of the women who were at high risk of OHSS in the GnRHa long protocol.…”

“…Our previous study demonstrated that high progesterone level did not appear to have a detrimental role in oocytes and embryos. 6,12 Although MPA was contraindicated in human pregnancy, a study following up 1893 liveborn infants born from HMG+MPA treatment found that it did neither compromised neonatal outcomes nor increase the prevalence of congenital malformations compared with short protocol and mild ovarian stimulation. 18 In contrast, the GnRHa long protocol has been generally reorganized and extensively used worldwide for IVF treatment.…”

Calcium infusion plus or minus cabergoline for prevention of ovarian hyperstimulation syndrome: Randomized double-blind placebo-controlled trial

“…In analysis of subgroup with irregular anovulatory cycle PCOS, authors reported a development of more severe OHSS when compared to less risk, women with regular ovulatory cycles [8] , so there is a need for adequate powered RCT to explore the antagonist protocol OHSS sparing effect in women at high risk for OHSS development; namely, with high basal Antimullerian hormone (AMH), Antral follicular count (AFC) and high SE2 at ovulation triggering. GnRh agonist ovulation triggering instead of HCG as OHSS protective strategy, despite it is only possible in non-agonist based protocols as antagonist protocols as well as recently introduced progesterone primed ovarian stimulation protocol (PPOS), [30,31,32,33] was less effective than HCG triggering as regards of ongoing pregnancy rate and live birth rate [26] as well as infertility clinician still preferred HCG over GnRh agonist in antagonist protocol [28] and that recent review of utilization of GnRh agonist as ovulation triggering instead of HCG stated that this issue still needs more research [29] .…”