Similar IVF outcomes reported for PPOS and GnRH antagonist protocols

Similar IVF outcomes reported for PPOS and GnRH antagonist protocols | Image Credit: © MedicalWorks - © MedicalWorks - stock.adobe.com.

A gonadotropin-releasing hormone (GnRH) antagonist protocol and a progesterone-primed ovarian stimulation (PPOS) protocol lead to similar outcomes in ovarian stimulation, according to a recent study published in Cureus.¹

Background on COS protocols

GnRH agonists and antagonists are used in controlled ovarian stimulation (COS) to suppress endogenous follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production. As freeze-all protocols are increasingly used, alternative methods such as PPOS protocols have been considered. This regimen is gained popularity in Japan because of a reduced number of hospital visits.²

“However, a drawback of PPOS is that it induces early decidualization of the endometrium, which precludes fresh embryo transfer. Therefore, it is predicated on the use of a freeze-all protocol,” wrote investigators.¹

Treatment details

The retrospective, observational study was conducted to compare ovarian response and pregnancy outcomes between PPOS and GnRH antagonist protocols using follitropin delta. Participants were Japanese women aged 20 to 45 years with preserved ovarian function and anti-Mullerian hormone of at least 0.8 nh/mL.

Additional inclusion criteria included body mass index between 18 and 30 kg/m³, a history of IVF with up to 3 oocyte retrievals, oocyte retrieval by a skilled physician, and freeze-all cycles. Participants underwent stimulation on the second or third day of the menstrual cycle.

Patients undergoing the GnRH antagonist protocol achieved endogenous LH suppression through subcutaneous injections of cetrorelix. This process was performed from day 5 or 6 of COS to ovulation triggering.

A 10 mg dydrogesterone oral dose was administered twice per day between stimulation and the day of trigger in patients undergoing the PPOS cycle. All participants underwent blood sample and transvaginal ultrasound collection prior to medication administration and on stimulation days 6, 8 to 10, and the day of the trigger.

Oocyte retrieval and endometrial assessment

Oocytes were obtained approximately 36 hours after induction of final oocyte maturation with a GnRH agonist bolus. Conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection was used to perform fertilization on the same day.

Investigators measured endometrial thickness in patients at approximately day 14 of the menstrual cycle. Those with a thickness of 8 mm or greater received a progesterone suppository vaginally.

Pregnancy rates were reported as the primary outcome, while the number of oocytes and blastocyst formation rate were reported as secondary outcomes. Investigators combined accumulated data from GnRH antagonist cycles and PPOS cycles. A stratified analysis based on age group was also performed.

Cycle characteristics

There were 149 GnRH antagonist cycles and 147 PPOS cycles included in the final analysis. No significant variations in baseline characteristics were observed based on the cycle performed, except for increased FSH level in the PPOS group.

In the GnRH antagonist cycle, 8.9±6.4 oocytes were collected, vs 9.4±5.6 oocytes in the PPOS cycle. These groups also had 3.4±3.2 4.1±3.2 blastocysts formed, respectively. This indicated increased blastocysts formed in the PPOS cycle vs the GnRH antagonist cycle, but no significant difference in the number of retrieved oocytes.

Age-stratified analysis

When stratifying by age, 10.9±5.6 oocytes were obtained in patients aged under 35 years in the GnRH antagonist cycle, vs 11.7±6.3 in the PPOS cycle. The number of blastocytes formed in this age group were 4.7 ± 5.4 vs 5.4 ± 3.1, respectively.

In patients aged 35 to 39 years, the number of oocytes obtained were 8.7 ± 7.4 vs 9.1 ± 5.4, respectively, while the number of blastocytes formed were 3.2 ± 3.5 vs 4.2 ± 3.3, respectively. Finally, the number of oocytes obtained were 6.4 ± 4.4 vs 7.6 ± 4.7, respectively, in those aged 40 years or older, while the number of blastocytes formed were 2.2 ± 0.4 vs 2.7 ± 2.3, respectively.

Pregnancy outcomes

This data highlighted no significant differences in the number of oocytes received based on age group, while the number of blastocytes formed was higher in PPOS cycles among patients aged 35 to 39 years. For the primary outcome, clinical pregnancy was reported in 66.7% of patients in the GnRH antagonist cycle vs 63.2% in the PPOS cycle.

Ongoing pregnancy rates were 66.7% vs 55.2%, respectively. This data highlighted no significant differences in clinical or ongoing pregnancy rates between cycles.

“By analyzing a substantial dataset from a single IVF clinic over a 2-year period, the study demonstrates that while pregnancy rates were comparable between the two protocols, the PPOS protocol showed a trend toward improved oocyte and blastocyst outcomes across all age groups,” wrote investigators.

References

1. Hanaoka M, Hanaoka K, Yamada M. Ovarian responses and outcomes of in vitro fertilization following progesterone-primed ovarian stimulation and gonadotropin-releasing hormone (GnRH) antagonist protocols using follitropin delta. Cureus. 2025. doi:10.7759/cureus.85341
2. Ozawa N, Iwami N, Kawamata M, et al. Comparison of clinical outcomes of progestational ovulation induction (PPOS) using follitropin Delta by time of initiation of progestational hormone. J Fertil Implant. 2024;41:178-86.