Abstract
Study question
To compare the impact on oocyte quality and reproductive outcomes in patients who received oocytes from donors stimulated with MPA versus GnRH antagonist protocol.
Summary answer
Compared to GnRH antagonist, MPA does not exert a major effect on oocyte quality and yields similar reproductive outcomes in egg donation recipients.
What is known already
Conventional ovarian stimulation (OS) protocols have classically used GnRH analogues, both agonists and antagonists, to avoid premature follicular luteinization. The oral administration of MPA or micronized progesterone during the follicular phase of OS has emerged as an attractive alternative to conventional protocols in the prevention of early luteinization. Compared to progesterone, MPA is characterized by a moderate-strong progestanic action, lower androgenic properties and does not interfere with the measurement of endogenous progesterone. In our group, administration of MPA during the follicular phase of OS has been included in the routine clinical practice of our donor program since late 2019.
Study design, size, duration
Multicentre, retrospective, observational, cohort study carried out in eleven private university-affiliated IVF centers. The present study included a total of 14,282 fresh ovum donation cycles performed from October 2017 to March 2020. Oocyte donors were recruited and stimulated under either MPA (n = 4,665) or GnRHa (n = 9,617) to suppress the pituitary during the follicular phase of OS, and GnRH agonist was administered to trigger final oocyte maturation in all the participants.
Participants/materials, setting, methods
Recipients were divided according to the protocol used for premature luteinization prevention during the follicular phase of the ovum donation matched-cycle: Group 1, recipients who received oocytes from donors treated with 10 mg/day of MPA (ProgeveraÒ); Group 2, recipients who received oocytes from GnRH antagonist (FyremadelÒ) down-regulated donor cycles. All the procedures were approved by an Institutional Review Board (1910-VLC–091-JG) and complied with Spanish law on assisted reproductive technologies (14/2006).
Main results and the role of chance
Regarding donoŕs baseline characteristics, age and antral follicle count were significantly different between groups, but not clinical differences. The length of ovarian stimulation was similar in both groups (10.7 days [95% Confidence Interval (CI) 10.5–10–8] vs 10.5 days [95% CI 10.0–11.00]). Despite slightly higher mean total dose of FSH administered in Group 1 compared to Group 2 (1.841 IU [95% CI 1.813–1.868] vs 1.739 IU [95% CI 1.723–1.754]), there were no differences in the total dose of hMG administered between both groups (967 IU [95% CI 901–1.034] vs 971 IU [95% CI 944–998]). With regard to IVF data, both the number of retrieved oocytes (22.9 [95% CI 22.4–23.4] vs 24.1 [95% CI 23.8–24.3]), and mature oocytes (18.7 [95% CI 18.3–19.1] vs 19.3 [95% CI 19.1–19.6]), were slightly lower in Group 1 compared to Group 2, whereas fertilization rate was significantly higher in Group 1 compared to Group 2 (82.1% [95% CI 81.7–82.6] vs 80.8% [95% CI 80.6–81.2]),. Regarding the clinical outcomes, no differences were observed in either implantation rate (58.7% [95% CI 56.7–60.7] vs 59.3% [95% CI 57.3–61.3]) or clinical pregnancy rate (59.5% vs 59.8%, P = 0.04) between both groups.
Limitations, reasons for caution
As a consequence of being a retrospective study, only association, and not causation, can be inferred from the results. A further limitation is that donors are healthy young women and do not perfectly match other populations, as infertile patients who may be older, low or high responders to OS.
Wider implications of the findings: MPA emerges as an effective oral alternative to GnRH analogues for preventing premature luteinizing hormone surges in donors undergoing OS in ovum donation program. Compared with GnRH antagonists, MPA has advantages of being an oral administration route and providing easy access, yielding similar clinical results.
Trial registration number
1910-VLC–091-JG
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