Progestin-primed milder stimulation with clomiphene citrate yields fewer oocytes and suboptimal pregnancy outcomes compared with the standard progestin-primed ovarian stimulation in infertile women with polycystic ovarian syndrome

Abstract

BackgroundOral progestin has recently been used to prevent premature LH surges in ovarian stimulation, and this progestin-primed ovarian stimulation (PPOS) is effective and safe in patients with different ovarian reserves. The current data are lacking regarding how to individualize the gonadotropin dose and regimen for women with polycystic ovarian syndrome (PCOS). A retrospective cohort trial was performed to evaluate the efficacy of progestin-primed milder stimulation with clomiphene citrate (CC) compared to the standard progestin-primed ovarian stimulation (PPOS) protocol for infertile women with PCOS.MethodsA total of 220 PCOS women were collected and classified into the study group (HMG 150 IU/d + CC 50 mg/d + MPA 10 mg/d) and control group (HMG 225 IU/d + MPA 10 mg/d). Ovulation was triggered by GnRH agonist 0.1 mg and hCG 1000 IU when dominant follicles matured. Viable embryos were cryopreserved for later transfer. The primary endpoint was the ongoing pregnancy rate. Secondary outcomes included the cycle characteristics and the live birth rate.Result(s)The study group consumed less HMG (1470.0 ± 360.1 IU vs 1943.8 ± 372.0 IU, P < 0.001) and harvested fewer oocytes than the control group (12.2 ± 7.4 vs 18.2 ± 9.7, P < 0.001). The study group showed a higher mid-follicular LH concentration (4.49 ± 2.49 mIU/ml vs 2.52 ± 2.09 mIU/ml, P < 0.05) but no endogenous LH surge. No between-group difference was found in the incidence of ovarian hyperstimulation syndrome (OHSS) (0.91% vs 0.91%, P > 0.05). The cumulative ongoing pregnancy rate and live birth rate per patient were lower but did not reach significance compared with the control group (71.8% vs 81.8 and 64.5% vs 75.5%, respectively, both P > 0.05).Conclusion(s)The milder PPOS with CC in PCOS women led to lower oocyte yields and suboptimal pregnancy outcomes compared to the standard PPOS treatment. The two regimens both achieved a low incidence of OHSS. The results from the CC combination regimen provide a new insight for developing a more patient-friendly protocol for PCOS women.

Progestin-Primed Ovarian Stimulation with Clomiphene Citrate Supplementation May Be More Feasible for Young Women with Diminished Ovarian Reserve Compared with Standard Progestin-Primed Ovarian Stimulation: A Retrospective Study

“…CC interacts with hypothalamic estrogen receptors and increases endogenous FSH and LH secretion by blocking the estrogen-negative feedback mechanism. 11 , 24 , 25 Our data are consistent with previous findings 5 , 6 and showed that LH levels on days 7–10 and the day of trigger in PPOS+CC were significantly higher than in all subgroups of standard PPOS ( P < 0.05). Furthermore, the E 2 levels and P levels on trigger day were significantly higher in PPOS+CC than in standard PPOS ( P < 0.01).…”

“… 11 , 12 PPOS supplemented with CC (PPOS+CC) significantly reduces the occurrence of profound pituitary suppression in women with normal ovarian reserve or polycystic ovarian syndrome, and the combination treatment is likely to reduce Gn consumption compared with PPOS treatment alone. 5 , 6 …”

Validation of an extremely patient-friendly progestin-primed ovarian stimulation protocol in normal and high responders by comparing with conventional antagonist protocol: a retrospective study

“…In these regimens both GnRH antagonists and endogenous progesterone exerted suppressive influence and consequently resulted in much more profound pituitary suppression and therefore much higher dosage of FSH or longer stimulation duration. Long-acting FSH has also been used in a fashion of random start with antagonist protocol [26], but there is lack of investigation specific to luteal stimulation. As for PPOS without GnRH antagonist, the group in China led by Kuang [8,10,27 Almost all previous relevant studies unanimously required higher dosage of HMG with or without longer duration for stimulation in MPA-PPOS [8,12,33].…”

Validating the Use of Corifollitropin Alfa in Progestin-Primed Ovarian Stimulation Protocol on Normal and High Responders by Comparing with Conventional Antagonist Protocol: A Retrospective Study

“…The difference might emerge in low responders stimulated with only FSH instead of HMG or FSH + LH. On the other hand, it seems that clomiphene co-administration is able to avoid LH oversuppression in PPOS, which resulted in an initial slight rise followed by a downward trend in LH, although the limited data came from normal responders [33] and high responders [34]. If we consider extending our long-acting FSH PPOS application to low responders, different progestin and clomiphene combinations might be necessary in PPOS with long-acting FSH where no exogenous LH is given in the first week.…”