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

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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Progestin primed ovarian stimulation using corifollitropin alfa in PCOS women effectively prevents LH surge and reduces injection burden compared to GnRH antagonist protocol

Scientific Reports ◽

10.1038/s41598-021-02227-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ting-Chi Huang ◽

Mei-Zen Huang ◽

Kok-Min Seow ◽

Ih-Jane Yang ◽

Song-Po Pan ◽

...

Keyword(s):

Clinical Outcomes ◽

Gnrh Agonist ◽

Ovarian Stimulation ◽

Gnrh Antagonist ◽

Polycystic Ovary ◽

Implantation Rate ◽

Live Birth Rate ◽

Lh Surge ◽

Corifollitropin Alfa ◽

Premature Lh Surge

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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P–685 Luteinization after final oocyte maturation induction is not compromised in women that receive double dose of Gonadotrophin-releasing hormone antagonists during controlled ovarian hyperstimulation

Human Reproduction ◽

10.1093/humrep/deab130.684 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

M Luna ◽

T Alkon ◽

D Cassis ◽

C Hernandez-nieto ◽

B Sandler

Keyword(s):

Oocyte Maturation ◽

Gnrh Antagonist ◽

Controlled Ovarian Hyperstimulation ◽

Ovarian Hyperstimulation ◽

Double Dose ◽

Gnrh Antagonists ◽

Lh Surge ◽

Final Oocyte Maturation ◽

Serum Hormone ◽

Premature Lh Surge

Abstract Study question Does the use of double dose of GnRH antagonists during COH in women with risk of premature LH surge alter luteinization after final oocyte maturation induction? Summary answer The use of double dose of GnRH antagonist in women with risk of premature luteinizing hormone surge dosent affect luteinization after final oocyte maturation induction. What is known already GnRH antagonists are used to prevent a premature LH surge during controlled ovarian hyperstimulation. The antagonists directly inhibit gonadotrophin release within several hours through competitive binding to pituitary GnRH receptors, producing a rapid suppression of LH and FSH, with no initial flare effect. In women with diminished ovarian reserve (DOR) it is not uncommon that premature luteinization cannot be completely prevented using a daily dose GnRH antagonist. To date, no study has evaluated the effects of using a daily double dose of GnRH antagonists to prevent a premature LH surge and its effect on luteinization after final oocyte maturation induction. Study design, size, duration This monocentric retrospective analysis evaluated the effect on luteinization after final oocyte maturation induction in twenty women during COH who received a daily double dose of GnRH antagonists (Cetrotide 0.25 mg/mL, Merck) from January 2020 to December 2020. Participants/materials, setting, methods Women with severe DOR and history of premature luteinization during COH received a double dose of GnRH antagonist when the leading follicle reached 12–14 mm (am and pm). When two follicles reached ≥18 mm in diameter, final oocyte maturation was induced with dual trigger using Leuprolide acetate and hCG. Progesterone, estradiol, bHCG, and LH levels were measured the day after final oocyte maturation induction to assure adequate luteinization. Main results and the role of chance In total twenty women were included in the analysis. Mean age 36.8± 4.2, AMH 0.65± 0.32 ng/ml, baseline antral follicle count 4± 2.3, serum hormone levels the day of ovulation induction trigger: progesterone 0.89± 0.34 ng/ml, LH 1.6± 2.1 ng/ml, estradiol 1235 ± 1420 pg/ml. Post-surge serum hormone levels average reached adequate levels: estradiol 1645 ± 1116 pg/ml, progesterone 20.4 ±2.2 ng/ml, LH 62.66± 10.5 IU/ml and, bHCG 247±115 IU/ml. A total of 76 oocytes were retrieved (3.8± 0.8 oocytes per patient), 63.1% (48/76) MII, 22% (17/76) MI, 14% (11/76) GV. Limitations, reasons for caution The retrospective nature of the study, small sample size, and potential variability in the study center’s laboratory protocol(s) compared to other reproductive treatment centers may limit the external validity of our findings. Wider implications of the findings: The daily use of double dose of GnRH antagonists during COH offers the possibility of preventing a premature LH surge in women with DOR with high risk of early ovulation, without compromising luteinization after final oocyte maturation induction. Trial registration number NA

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New protocol for commencing the GnRH antagonist in assisted conception treatment cycles: elimination of the premature LH surge with similar pregnancy rates

Reproduction Nutrition Development ◽

10.1051/rnd:2004059 ◽

2004 ◽

Vol 44 (6) ◽

pp. 565-570 ◽

Cited By ~ 1

Author(s):

Andreas Mavrides ◽

Stuart Lavery ◽

Geoffrey Trew

Keyword(s):

Gnrh Antagonist ◽

Pregnancy Rates ◽

Assisted Conception ◽

Lh Surge ◽

Premature Lh Surge

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Low dose human chorionic gonadotropin may be a cost effective alternative to human menopausal gonadotropin for ovarian stimulation during in vitro fertilization cycles

Fertility and Sterility ◽

10.1016/j.fertnstert.2013.07.1093 ◽

2013 ◽

Vol 100 (3) ◽

pp. S260

Author(s):

T. Pakrashi ◽

H. Baydoun ◽

S. Taylor ◽

S. Bocca ◽

L. Stadtmauer ◽

...

Keyword(s):

In Vitro Fertilization ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Ovarian Stimulation ◽

Low Dose ◽

Cost Effective ◽

Human Menopausal Gonadotropin ◽

Vitro Fertilization ◽

Cost Effective Alternative

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Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH)-antagonist Cetrorelix at different dosages

Journal of Assisted Reproduction and Genetics ◽

10.1007/bf02065939 ◽

1996 ◽

Vol 13 (3) ◽

pp. 216-222 ◽

Cited By ~ 40

Author(s):

R. Felberbaum ◽

T. Reissmann ◽

W. Küpker ◽

S. Al-Hasani ◽

O. Bauer ◽

...

Keyword(s):

Ovarian Stimulation ◽

Gnrh Antagonist ◽

Concomitant Administration ◽

Gonadotropin Releasing Hormone ◽

Human Menopausal Gonadotropin ◽

Releasing Hormone

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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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