P-609 Comparison of fixed and flexible progestin primed ovarian stimulation protocols to prevent luteinizing hormone surge in poor ovarian response
Authors: Doğan Durdağ G , Çağlar Aytaç P , Alkaş Yağınç D , Yetkinel S , Çok T , Şimşek E 
Published: June 2022

Abstract

Study question
Are fixed and flexible progestin primed ovarian stimulation (PPOS) protocols comparable in preventing luteinizing hormone (LH) surge in poor response group?

Summary answer
Both PPOS protocols are comparable in preventing LH surge in poor response group. Fertilization and clinical pregnancy rates are also similar.

What is known already
PPOS protocols are recently used as an alternative to gonadotropin releasing hormone (GnRH) antagonists for pituitary suppression. Oral administration and lower costs of progestins are advantageous, while fresh embryo transfer is precluded due to high progesterone exposure and impaired endometrial receptivity. However, PPOS protocol is shown to be effective at planned all-freeze cycles in different patient populations. Recently progestins are also shown to prevent LH surge when administered in later phase of the cycle. Namely, flexible protocols are based on the follicle size or hormone values. Few studies compared flexible PPOS protocols with GnRH antagonist protocols, and declared similar outcomes.

Study design, size, duration
This retrospective cohort study was conducted in a single center, including the PPOS cycles of poor response patients in 3 years period, between January 2019 and December 2021.

Participants/materials, setting, methods
A hundred sixteen poor ovarian response patients who were administered PPOS protocols for pituitary suppression were included. Eighty-six patients received fixed protocol, where 20 mg/day dydrogesterone was started in cycle day 3 along with gonadotropins and continued until trigger day, while thirty patients received flexible protocol, where 20 mg/day dydrogesterone was started when the leading follicle reached 14 mm or in stimulation day 6. Descriptive features and cycle characteristics of the two groups were evaluated.

Main results and the role of chance
Indications for PPOS protocol included diminished ovarian reserve and poor ovarian response. Baseline characteristics including age, antral follicle count, anti mullerian hormone levels, and infertility period were similar in both groups (p &gt; 0.05), while body mass index was higher in the flexible protocol group (median values were 23.3(16.8-35.9) and 26.6(19.4-35.8) kg/m2, in fixed and flexible groups respectively, p = 0.004). Cycle parameters including total days of gonadotropin administration, total gonadotropin dose, progesterone and estradiol values and endometrial thickness at trigger day were similar (p &gt; 0.05). Retrieved oocytes numbers and metaphase II oocyte numbers were higher in the fixed protocol group, however 2PN numbers were similar (p = 0.030, 0.013 and 0.079, respectively). LH surge, which was demonstrated by progesterone value higher than 1.2 ng/mL on trigger day, occured at 5.8% and 6.7% patients in fixed and flexible PPOS protocols, respectively (p = 1.000). Clinical pregnancy rates were 64.1% in fixed protocol and 42.9% in flexible protocol groups, which were also statistically similar (p = 0.407).

Limitations, reasons for caution
Retrospective nature and small number of patients together with unbalanced numbers of cases in the two groups are the limitations of the study.

Wider implications of the findings
Flexible PPOS protocol has been studied recently, and necessitate further prospective research. It seems to be a patient friendly stimulation protocol, however, studies, particularly on certain subgroups such as diminished ovarian reserve should be conducted to elucidate its effectiveness.

Trial registration number
not applicable