P-278 The impact of previous pituitary suppression protocols on IVF outcomes in patients with endometriosis undergoing freeze-all approach
Authors: Tohma Y  A , Boynukalin K , Gultomruk M , Akkaya C  M , Yarkiner Z , Bahceci M , Bozdag G 
Published: July 2024

Study question

Do embryological parameters and live birth rates differ in patients with endometriosis undergoing freeze-all approach when GnRH-antagonist protocol or progestin primed pituitary suppression(PPOS) was preferred?

Summary answer

When comparing the GnRH antagonist protocol, the PPOS protocol was associated with more usable cleavage stage embryos but with a similar live birth rate.

What is known already

Optimal COH protocol for patients with endometriosis is still controversial. Initially, the GnRH agonist protocol was hypothesized to be superior because it was assumed to increase pregnancy rates by improving the inflammatory process of endometriosis. However, available data represented similar pregnancy rates in GnRH antagonist and GnRH agonist protocols. Recently, progestins have been used for suppression of endogenous LH surge instead of GnRH analogs in COH for various indications. Since, recent data indicates that utilization of progestins for more than eight days can reduce the inflammatory process of endometriosis, PPOS protocol might be employed in this patient group.

Study design, size, duration

This retrospective cohort study conducted at Bahçeci Health Group between January 2021-January 2023. Inclusion criteria were female age between 20-44 years, patients with endometrioma diagnosed by transvaginal ultrasonography and freeze-all cycles. Exclusion criteria were pre-implantation genetic testing (PGT) cycles, patients with uterine myoma distorting the endometrial cavity, congenital uterine anomaly and presence of hydrosalpinx.Each patient was included only once. A total of 607 patients;407 in GnRH antagonist group and 200 in PPOS group were recruited.

Participants/materials, setting, methods

The study analyzed the embryological parameters and live birth rates undergoing freeze-all cycles. COH was performed with recombinant FSH or HMG at a starting dose 150-300 IU depending on ovarian reserve and body mass index (BMI). LH surge was controlled by a flexible GnRH antagonist or fixed PPOS protocol. Primary outcome for embryological parameters were usable cleavage embryo after OS and live birth after the first frozen embryo transfer (FET) cycles.

Main results and the role of chance

Female age in PPOS group was older than GnRH antagonist group (33.3±4.9 vs.32.4±4.8,p=0,02).Other demograhic characteristics were similar among two groups.Total gonadotrophin dose and duration of stimulation in PPOS group were lower than antagonist group (2602.3±1083.5 vs.2866.9±1147.9 IU, p = 0,002 and 10.86±1.77 vs. 11.59±1.82 days, p &lt; 0.001). No significant difference regarding endocrinological parameters of OS and number of oocytes retrieved, mature oocyte, maturation and fertilization rates was found in two groups. However, the number of day 3 usable embryos were higher in the PPOS group than GnRH antagonist group (4.66±4.38 vs. 3.84±3.72 p = 0.04). There was no difference in the cancellation rates. A total of 478 FET cycles of 607 were evaluated; 323 in GnRH antagonist and 255 in PPOS group. No significant difference in FET cycle and embryological characteristics was found in two groups. The clinical pregnancy rate, miscarriage rate, live birth rate and multiple pregnancy rates per transfer were comparable between the two groups [59.1% (191/323) vs. 59.4% ( 92/155) p = 0,963;17.3%(33/191) vs 0.9%(10/92) p = 0,16; 48.6%(157/323) vs. 52.9% (82/155) p = 0,379; 7.3%(14/191) vs.10.9% (10/92) p = 0317, respectively].Multivariate binary regression analysis revealed that female age, embryo day embryo quality.number of embryos transferred were significant independent factors for live birth but not the PPOS vs GnRH antagonist.

Limitations, reasons for caution

Although we used regression models to adjust all possible confounders, it was a retrospective study with its intrinsic limitations. Further prospective RCTs are warranted.

Wider implications of the findings

Although cleavage stage usable embryo was significantly higher in PPOS group,the pregnancy outcomes were comparable between groups.Those results suggest that theoretical advantages of progestin in preceding OS does not seem to present a significant difference on live birth,but should be confirmed with prospective trials within cohort of women with endometriosis.

Trial registration number

not applicable ( retrospective study)