Exogenous progesterone for LH surge prevention is redundant in ovarian stimulation protocols

AbstractUtilizing corifollitropin alfa in GnRH antagonist (GnRHant) protocol in conjunction with GnRH agonist trigger/freeze-all strategy (corifollitropin alfa/GnRHant protocol) was reported to have satisfactory outcomes in women with polycystic ovary syndrome (PCOS). Although lessening in gonadotropin injections, GnRHant were still needed. In addition to using corifollitropin alfa, GnRHant was replaced with an oral progestin as in progestin primed ovarian stimulation (PPOS) to further reduce the injection burden in this study. We try to investigate whether this regimen (corifollitropin alfa/PPOS protocol) could effectively reduce GnRHant injections and prevent premature LH surge in PCOS patients undergoing IVF/ICSI cycles. This is a retrospective cohort study recruiting 333 women with PCOS, with body weight between 50 and 70 kg, undergoing first IVF/ICSI cycle between August 2015 and July 2018. We used corifollitropin alfa/GnRHant protocol prior to Jan 2017 (n = 160), then changed to corifollitropin alfa/PPOS protocol (n = 173). All patients received corifollitropin alfa 100 μg on menstruation day 2/3 (S1). Additional rFSH was administered daily from S8. In corifollitropin alfa/GnRHant group, cetrorelix 0.25 mg/day was administered from S5 till the trigger day. In corifollitropin alfa/PPOS group, dydrogesterone 20 mg/day was given from S1 till the trigger day. GnRH agonist was used to trigger maturation of oocyte. All good quality day 5/6 embryos were frozen, and frozen-thawed embryo transfer (FET) was performed on subsequent cycle. A comparison of clinical outcomes was made between the two protocols. The primary endpoint was the incidence of premature LH surge and none of the patients occurred. Dydrogesterone successfully replace GnRHant to block LH surge while an average of 6.8 days of GnRHant injections were needed in the corifollitropin alfa/GnRHant group. No patients suffered from ovarian hyperstimulation syndrome (OHSS). The other clinical outcomes including additional duration/dose of daily gonadotropin administration, number of oocytes retrieved, and fertilization rate were similar between the two groups. The implantation rate, clinical pregnancy rate, and live birth rate in the first FET cycle were also similar between the two groups. In women with PCOS undergoing IVF/ICSI treatment, corifollitropin alfa/PPOS protocol could minimize the injections burden with comparable outcomes to corifollitropin alfa/GnRHant protocol.

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Dose-Dependent Chlormadinone Acetate Can Suppress Premature LH Surge in Parallel with LH Value Reduction

Fertility & Reproduction ◽

10.1142/s2661318220500048 ◽

2020 ◽

Vol 02 (01) ◽

pp. 21-26

Author(s):

Yuya Takeshige ◽

Tomoko Hashimoto ◽

Koichi Kyono

Keyword(s):

Ovarian Stimulation ◽

Gnrh Antagonist ◽

Cost Effective ◽

Human Menopausal Gonadotropin ◽

Retrospective Case ◽

Lh Surge ◽

Chlormadinone Acetate ◽

Appropriate Treatment ◽

Premature Lh Surge ◽

Dose Dependent

Background: Progestin-primed ovarian stimulation (PPOS) protocol is reported as an alternative method of premature luteinizing hormone (LH) surge suppression. How much dosage of chlormadinone acetate (CMA), a synthetic progestin, is appropriate treatment for this phenomenon? Methods: Retrospective case control study was performed at private assisted reproductive technology (ART) clinic in Japan. Collected data was 231 cycles in patients who underwent either PPOS protocol using 12, 6, 4, or 2 mg of CMA, groups 6C, 3C, 2C, and 1C, respectively (total, 113 cycles), or gonadotropin-releasing hormone (GnRH) antagonist protocol, groups 6A, 3A, 2A, and 1A, respectively (total, 118 cycles). In the CMA group, CMA and human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) were administered simultaneously beginning on menstrual cycle day 3. Serum P, E2, and LH were determined on the day of human chorionic gonadotropin (hCG) administration. Occurrence of premature LH surge was compared between two groups. Pregnancy outcomes were also calculated. Results: Premature LH surge was completely suppressed in CMA groups 6C, 3C, and 2C. On the other hand, this phenomenon was detected in antagonist method groups (5.9%, 7/118). But spontaneous ovulation was not observed in any group, and clinical outcomes are equal to those of GnRH antagonist treatment. Conclusions: Controlled ovarian stimulation (COS) using CMA can be an appropriate alternative progestin for PPOS protocol. Since CMA is an oral medication, this method can be easy to conduct and cost-effective compared with the antagonist method. From our observation, we suggest 4 mg/day of CMA can control the egg retrieval cycle without LH surge occurrence as in other PPOS methods.

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Evaluating the effect of ovarian stimulation and exogenous progesterone on CD31-positive cell density, VEGF protein, and miR-17-5p expression of endometrium immediately before implantation

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2020.110922 ◽

2021 ◽

Vol 133 ◽

pp. 110922

Author(s):

Soheila Salmasi ◽

Mohammadreza Sharifi ◽

Bahman Rashidi

Keyword(s):

Cell Density ◽

Ovarian Stimulation ◽

Exogenous Progesterone ◽

Vegf Protein

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Validating the Use of Corifollitropin Alfa in Progestin-Primed Ovarian Stimulation Protocol on Normal and High Responders by Comparing with Conventional Antagonist Protocol: A Retrospective Study

Life ◽

10.3390/life10060090 ◽

2020 ◽

Vol 10 (6) ◽

pp. 90

Author(s):

Chen-Yu Huang ◽

Guan-Yeu Chen ◽

Miawh-Lirng Shieh ◽

Hsin-Yang Li

Keyword(s):

Retrospective Study ◽

Ovarian Stimulation ◽

Live Birth Rate ◽

Fertilization Rate ◽

Stimulation Protocol ◽

Cleavage Rate ◽

Lh Surge ◽

Long Acting ◽

High Responders ◽

Antagonist Protocol

Our previous study showed a satisfactory reproductive outcome resulting from the patient-friendly ovarian stimulation protocol using long-acting follicle stimulation hormone (FSH) plus oral medroxyprogesterone acetate (MPA). The present retrospective study aims to compare the efficacy of the patient-friendly ovarian stimulation protocol with that of the antagonist protocol on normal and high responders aged between 24 and 39 years in a tertiary fertility center in Taiwan. To prevent premature luteinizing hormone (LH) surge, oral MPA was given to patients in group 1 (n = 57), whereas antagonist protocol was applied to group 2 (n = 53). Duration and dosage of stimulation, number of injections and visits before trigger, incidence of premature LH surge, number of oocytes retrieved, fertilization rate, cleavage rate, rate of good embryos available, incidence of ovarian hyperstimulation syndrome, cumulative clinical pregnancy rate and live birth rate per retrieval were compared between groups. We conclude that our patient-friendly ovarian stimulation protocol with MPA demonstrates satisfactory stimulation and reproductive outcomes that are comparable to those of an antagonist protocol.

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Effect of endogenous and exogenous progesterone on the oestradiol-induced LH surge in dairy cows

Reproduction ◽

10.1530/jrf.0.0840367 ◽

1988 ◽

Vol 84 (1) ◽

pp. 367-371 ◽

Cited By ~ 7

Author(s):

A. S. Nanda ◽

W. R. Ward ◽

H. Dobson

Keyword(s):

Dairy Cows ◽

Lh Surge ◽

Exogenous Progesterone

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Alternative approaches to ovarian stimulation for IVF

Reproductive Medicine Review ◽

10.1017/s096227990100014x ◽

2001 ◽

Vol 9 (1) ◽

pp. 77-89 ◽

Cited By ~ 3

Author(s):

NS Macklon ◽

BCJM Fauser

Keyword(s):

Ovarian Stimulation ◽

Repeated Administration ◽

Vitro Fertilization ◽

Serum Luteinizing Hormone ◽

Gonadotrophin Releasing Hormone ◽

Exogenous Progesterone ◽

Oocyte Meiotic Maturation ◽

Late Follicular Phase ◽

Single Bolus Injection

Ovarian stimulation protocols applied world-wide today may take several weeks per stimulated cycle, are complex, expensive and associated with a certain degree of risk. Gonadotrophin preparations are administered to stimulate multiple follicle development usually at daily doses of 150–300 IU (and sometimes higher) for one to three weeks. A premature rise in serum luteinizing hormone (LH) levels, generally believed to be detrimental for in vitro fertilization (IVF) outcome, is prevented by the co-administration of a gonadotrophin-releasing hormone (GnRH) agonist. This is usually initiated in the preceding cycle to allow for pituitary downregulation to occur before the initiation of exogenous follicle-stimulating hormone (FSH). Finally, the resumption of oocyte meiotic maturation is induced by a single bolus injection of human chorionic gonadotrophin (hCG) during the late follicular phase. In addition, the corpus luteum is supported during the luteal phase by repeated administration of hCG or supplemented by exogenous progesterone.

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Comparison of Cumulative Live Birth Rates Per Aspiration IVF/ICSI Cycle Between GnRH Antagonist Protocol and Progesterone-Primed Ovarian Stimulation Protocol for Infertility With Normal Ovarian Reserve: A Randomised Controlled Trial

10.21203/rs.3.rs-927208/v1 ◽

2021 ◽

Author(s):

Hongjuan Ye ◽

Xue Xue ◽

Liya Shi ◽

Ying Qian ◽

Hui Wang ◽

...

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Ovarian Reserve ◽

Ovarian Stimulation ◽

Gnrh Antagonist ◽

Controlled Trial ◽

In Vitro Fertilisation ◽

Gnrh Antagonists ◽

Lh Surge ◽

Cumulative Live Birth

Abstract Background: Oral progestin has been used to prevent premature ovulation during follicle stimulation protocols performed in combination with a freeze-only strategy. However, no studies have determined how oral progestin clinically compares to gonadotropin-releasing hormone (GnRH) antagonists in women with normal ovulation. This study aimed to compare the efficacy and safety of controlled ovarian stimulation between progestin-primed ovarian stimulation (PPOS) protocol and GnRH antagonist (GnRH-ant) protocol.Methods: Young women with infertility and normal ovarian reserve who underwent in vitro fertilisation (IVF) treatments were screened and randomly allocated to the PPOS or GnRH-ant group. Women in the PPOS group underwent freeze-all and delayed embryo transfer, whilst fresh embryo transfer was preferred for those in the GnRH-ant group. The primary endpoint was the cumulative live birth rate (CLBR). Secondary endpoints included the incidence of premature luteinising hormone (LH) surge and the number of viable embryos.Results: CLBRs were similar in the PPOS and GnRH-ant group (55.75% vs. 52.87%, respectively, P > 0.05). No premature LH surge was observed during ovarian stimulation in the PPOS group, although six (3.45%) cases were observed in the GnRH-ant group. On the trigger day, LH level was lower in the PPOS group than in the GnRH-ant group (2.30 ± 1.78 mIU/ml vs. 3.66 ± 3.52 mIU/ml, P < 0.01). There were no differences in the number of retrieved oocytes, mature oocytes, or viable embryos between the two groups. Other clinical outcomes including implantation rates (37.27% vs. 36.77%), clinical pregnancy rates (55.75% vs. 55.89%), and miscarriage rates (12.28% vs. 13.76%) were comparable between the PPOS group and GnRH-ant group (P > 0.05). There was also no significant differences in newborn weights for singleton or twin births between the two groups (P > 0.05).Conclusion: Live birth outcomes are similar for PPOS and GnRH antagonist protocols in women with normal ovarian reserve. PPOS is likely to play a promising role in the freeze-only strategy given its simplicity and convenience for the patient. Trial registration: This trial was registered in the China Clinical Trial Registry on September 6, 2018 (number: ChiCTR1800018246).

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