Serum progesterone is lower in ovarian stimulation with highly purified HMG compared to recombinant FSH owing to a different regulation of follicular steroidogenesis: a randomized controlled trial.

التفاصيل البيبلوغرافية
العنوان:	Serum progesterone is lower in ovarian stimulation with highly purified HMG compared to recombinant FSH owing to a different regulation of follicular steroidogenesis: a randomized controlled trial.
المؤلفون:	Bosch E; IVIRMA Global Research Alliance, IVIRMA Valencia, Valencia, Spain.; IVI Foundation, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, Valencia, Spain., Alamá P; IVIRMA Global Research Alliance, IVIRMA Valencia, Valencia, Spain.; IVI Foundation, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, Valencia, Spain., Romero JL; IVIRMA Global Research Alliance, IVIRMA Valencia, Valencia, Spain., Marí M; IVIRMA Global Research Alliance, IVIRMA Valencia, Valencia, Spain., Labarta E; IVIRMA Global Research Alliance, IVIRMA Valencia, Valencia, Spain.; IVI Foundation, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, Valencia, Spain., Pellicer A; IVI Foundation, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, Valencia, Spain.; IVIRMA Global Research Alliance, IVIRMA Rome, Roma, Italy.
المصدر:	Human reproduction (Oxford, England) [Hum Reprod] 2024 Feb 01; Vol. 39 (2), pp. 393-402.
نوع المنشور:	Randomized Controlled Trial; Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Oxford University Press Country of Publication: England NLM ID: 8701199 Publication Model: Print Cited Medium: Internet ISSN: 1460-2350 (Electronic) Linking ISSN: 02681161 NLM ISO Abbreviation: Hum Reprod Subsets: MEDLINE
أسماء مطبوعة:	Publication: Oxford, UK : Oxford University Press Original Publication: Oxford ; Washington, DC : Published for the European Society of Human Reproduction and Embryology by IRL Press, [c1986-
مواضيع طبية MeSH:	Progesterone* , Fertilization in Vitro*/methods, Pregnancy ; Female ; Humans ; Pregnancy Rate ; Estrone ; Follicle Stimulating Hormone, Human ; Ovulation Induction/methods ; Testosterone ; Pregnenolone
مستخلص:	Study Question: Does ovarian stimulation with highly purified (hp)-HMG protect from elevated progesterone in the follicular phase compared to recombinant FSH (r-FSH) cycles through a different regulation of follicular steroidogenesis? Summary Answer: hp-HMG enhanced the Δ4 pathway from pregnenolone to androstenodione leading to lower serum progesterone at the end of the cycle, while r-FSH promoted the conversion of pregnenolone to progesterone causing higher follicular phase progesterone levels. What Is Known Already: Elevated progesterone in the follicular phase has been related to lower clinical outcome in fresh IVF cycles. Progesterone levels are positively correlated to ovarian response, and some studies have shown that when r-FSH alone is used for ovarian stimulation serum progesterone levels on the day of triggering are higher than when hp-HMG is given. Whether this is caused by a lower ovarian response in hp-HMG cycles or to a difference in follicular steroidogenesis in the two ovarian stimulation regimens has not been well characterized. Study Design, Size, Duration: A randomized controlled trial including 112 oocyte donors undergoing ovarian stimulation with GnRH antagonists and 225 IU/day of r-FSH (n = 56) or hp-HMG (n = 56) was carried out in a university-affiliated private infertility clinic. Subjects were recruited between October 2016 and June 2018. Participants/materials, Setting, Methods: The women were aged 18-35 years with a regular menstrual cycle (25-35 days) and normal ovarian reserve (serum anti-Müllerian hormone (AMH) = 10-30 pMol/l) undergoing ovarian stimulation for oocyte donation. FSH, LH, estradiol (E2), estrone, progesterone, pregnenolone, 17-OH-progesterone, androstenodione, dehidroepiandrostenodione, and testosterone were determined on stimulation Days 1, 4, 6, and 8 and on day of triggering in serum and in follicular fluid. Samples were frozen at -20°C until assay. Total exposures across the follicular phase were compared by polynomic extrapolation. Main Results and the Role of Chance: Subjects in both groups were comparable in terms of age, BMI, and AMH levels. Ovarian response was also similar: 17.5 ± 7.9 (mean ± SD) versus 16.5 ± 7.5 oocytes with r-FSH and hp-HMG, respectively (P = 0.49). Serum progesterone (ng/ml) on day of trigger was 0.46 ± 0.27 in the hp-HMG group versus 0.68 ± 0.50 in the r-FSH group (P = 0.010). Differences for progesterone were also significant on stimulation days 6 and 8. The pregnenolone: progesterone ratio was significantly increased in the r-FSH group from stimulation day 8 to the day of trigger (P = 0.019). Serum androstenodione (ng/ml) on day of trigger was 3.0 ± 1.4 in the hp-HMG group versus 2.4 ± 1.1 in the r-FSH group (P = 0.015). Differences in adrostenodione were also significant on stimulation Day 8. The pregnenolone:androstenodione ratio was significantly higher in the hp-HMG group (P = 0.012) on Days 6 and 8 and trigger. There were no other significant differences between groups. Follicular fluid E2, FSH, LH, dehidroepioandrostenodione, androstenodione, and testosterone were significantly higher in the hp-HMG than r-FSH group. No differences were observed for progesterone, estrone, 17-OH-progesterone, and pregnenolone in follicular fluid. Limitations, Reasons for Caution: All women included in the study were young, not infertile, and had a normal BMI and a good ovarian reserve. The findings might be different in other patient subpopulations. Hormone analyses with immunoassays are subject to intra-assay variations that may influence the results. Wider Implications of the Findings: Stimulation with hp-HMG may prevent progesterone elevation at the end of the follicular phase because of a different follicular steroidogenesis pathway, regardless of ovarian response. This should be considered, particularly in patients at risk of having high progesterone levels at the end of the follicular phase when a fresh embryo transfer is planned. Study Funding/competing Interest(s): Roche Diagnostics provided unrestricted funding for all serum and follicular fluid hormone determinations. J.L.R., M.M., and A.P. have nothing to declare. E.B. has received consulting fees from Ferring, Merck, Gedeon Richter, and Roche and has participated in a research cooperation with Gedeon-Richter. In addition, the author has participated in speakers' bureau and received fees from Ferring, Gedeon Richter, Merck, and Roche. P.A. has received consulting fees from MSD and has participated in speakers' bureau and received fees from Ferring. P.A. also declares travel/meeting support from MSD. E.L. has received consulting fees from Ferring and MSD. In addition, the author has participated in a research cooperation with Gedeon-Richter. Also, the author has participated in speakers' bureau and received fees from Ferring and IBSA, as well as travel/meeting support from IBSA and Gedeon Richter. E.B., P.A., and E.L. also own stocks in IVIRMA Valencia. Trial Registration Number: NCT: NCT02738580. Trial Register Date: 19 February 2016. Date of First Patient’s Enrolment: 03 October 2016. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
معلومات مُعتمدة:	Roche Diagnostics
فهرسة مساهمة:	Keywords: HMG; elevated follicular phase progesterone; follicle development; ovarian stimulation; progesterone; recombinant FSH/ LH; steroidogenesis
سلسلة جزيئية:	ClinicalTrials.gov NCT02738580
المشرفين على المادة:	4G7DS2Q64Y (Progesterone) 2DI9HA706A (Estrone) 0 (Follicle Stimulating Hormone, Human) 3XMK78S47O (Testosterone) 73R90F7MQ8 (Pregnenolone)
تواريخ الأحداث:	Date Created: 20231201 Date Completed: 20240202 Latest Revision: 20240202
رمز التحديث:	20240202
DOI:	10.1093/humrep/dead251
PMID:	38037188
قاعدة البيانات:	MEDLINE

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تدمد:	1460-2350
DOI:	10.1093/humrep/dead251