Abstract Study question Micronized progesterone or GnRH antagonist: which is better to control the LH surge in the egg donation process? Summary answer Micronized progesterone is better. Is just as effective as GnRH antagonist and offers three additional advantages: cheaper, more convenient, and saves intermediate controls. What is known already GnRH antagonists have been widely considered to prevent LH surge. When fresh embryo transfer is not advised, micronized progesterone has been shown to be an effective alternative with some other very interesting advantages. If efficacy would prove to be similar, there will be three obvious advantages for the preferential use of micronized progesterone over the antagonist protocol: oral or vaginal administration is preferred over subcutaneous injection, cost would be much lower, and progesterone can be used from day one and avoid inconvenient intermediate controls. This would be particularly interesting in egg preservation, preimplantation genetic screening, and oocyte donation programs. Study design, size, duration We retrospectively analyzed our oocyte donation program from 2018 to 2021. All 358 cycles under short cycle protocol were studied. 67 donors were under the Antagonist cycle; age 24,7 years (18 – 32) with normal Body Max Index (22,2 Kg/m2 range 17-29) 291 donors were under the micronized progesterone cycle; age 24,5 years (18-31) with normal Body Max Index (22,3 Kg/m2 range 18-29) Participants/materials, setting, methods 67 donors were under the Antagonist cycle: LH suppression was accomplished by subcutaneous injections of Ganirelix 0.25 mg starting when follicles >14mm or E2 levels >400 pg/ml and continued until GnRH triggering. No patients were cancelled. 291 donors were under the micronized progesterone cycle: endogenous LH suppression was accomplished by vaginal administration of micronized progesterone (200 mg) once a day at bedtime, from stimulation day 1 and continuing until GnRH triggering. Four patients were cancelled. Main results and the role of chance 67 donors were under the GnRH antagonist cycle. 1115 oocytes were retrieved (16,6 range 2-39). All but two donors had egg vitrification: 65 patients, 916 oocytes (14,1 range 1-30) so 82% could be preserved. (916 / 1115). From 67 cycles, 916 vitrified oocytes were obtained (average 13,7). 291 patients were under the micronized progesterone cycle. Four patients were cancelled (no response in two, follicular asynchrony in one and personal reasons in one. No LH surges were observed). From 287 egg collections, 4683 oocytes were retrieved (16,3 range 2-49). All but two patients had vitrification: 285 patients, 3784 oocytes (13,3 range 2-37) so 81% could be preserved. (3784 / 4683). From 291 cycles, 3784 vitrified oocytes were obtained (average 13,2) Both groups were similar: total oocytes recovered per patient (16,3 vs 16,6) egg maturation (81 vs 82%) and global results (13,2 vs 13,7) Micronized progesterone offers three additional advantages: is obviously cheaper than GnRH antagonist. Also, vaginal route is commonly preferred to subcutaneous injections. And allows to offer a more flexible donor program making unnecessary to set some intermediate follicular controls. CONCLUSION: Micronized progesterone offers similar results than GnRH Antagonist with three additional advantages: is cheaper, is more convenient and intermediate controls can be avoided. Limitations, reasons for caution Although they are most likely similar, fertilization and pregnancy rates after both protocols should be deeply analyzed. Wider implications of the findings Micronized progesterone would also be particularly useful in egg preservation cycles and preimplantation genetic screening programs. Trial registration number not applicable
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