The efficacy of Clomiphene citrate in preventing a premature LH surge during controlled ovarian stimulation with human menopausal gonadotropins

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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Effects of Letrozole in Prevention of Premature Luteinizing Hormone (LH) Surge in Infertile Women with Clomiphene Citrate Resistant Polycystic Ovary Syndrome (PCOS) Undergoing Intrauterine Insemination

Galen Medical Journal ◽

10.31661/gmj.v4i3.232 ◽

2015 ◽

Vol 4 (3) ◽

pp. 104-11

Author(s):

Afsoon Zarei ◽

Tahere Bahrami Shabahrami ◽

Nasrin Dadras

Keyword(s):

Luteinizing Hormone ◽

Pregnancy Rate ◽

Polycystic Ovary ◽

Endometrial Thickness ◽

Intrauterine Insemination ◽

Clomiphene Citrate ◽

Control Group ◽

Lh Surge ◽

Significant Difference ◽

Premature Lh Surge

Background: Polycystic ovarian syndrome (PCOS) is among the important causes of infertility in young women. Premature luteinizing hormone (LH) surge (PLS) is one of its complications. PLS can reduce the quality of oocytes and therefore decrease the success of intrauterine insemination (IUI). Letrozole, a non-steroidal aromatase inhibitor, prevents LH surge. In this study, we aim to evaluate the effects of letrozole on preventing premature LH surge in clomiphene-resistant patients with PCOS undergoing IUI. Materials and Methods: In this randomized clinical trial, 131 patients who were developed with PCOS were selected for IUI cycle, divided into two groups randomly: control group (n=67) and letrozole group (n=64). Incidence of premature LH surge, pregnancy, abortion and ongoing pregnancy rate, endometrial thickness and number of follicles were measured in both groups. Results: No significant difference was seen between mean ages in the two groups; 11.9% of the control group and 21.9% of the letrozole group became pregnant (P =0.005); furthermore, premature LH surge was seen in 4.7% of the letrozole group and 8.9% of the control group (P =0.003). E2 and Endometrial thickness was higher in letrozole group; however, LH was significantly higher in the control group (P =0.026). Conclusion: Administration of letrozole in clomiphene-resistant patients with PCO undergoing IUI cycle can decrease the incidence of PLS. In addition, it can increase pregnancy rate significantly. Therefore, using letrozole is more reasonable in patients who have not responded to clomiphene or are hypersensitive. [GMJ.2015;4(3):104-11]

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Comparative Analysis of Effectiveness of Clomiphene Citrate and Letrozole Combined with Low Dose Human Menopausal Gonadotropin for Controlled Ovarian Stimulation in Intrauterine Insemination Cycles

Siriraj Medical Journal ◽

10.33192/smj.2021.26 ◽

2021 ◽

Vol 73 (3) ◽

pp. 198-203

Author(s):

Padmalaya Thakur ◽

Sujata Pradhan

Keyword(s):

Pregnancy Rate ◽

Ovarian Stimulation ◽

Low Dose ◽

Intrauterine Insemination ◽

Clomiphene Citrate ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Controlled Ovarian Stimulation ◽

Human Menopausal Gonadotropin ◽

Group B

Objective: To compare the efficacy of clomiphene citrate and letrozole in combination with low dose human menopausal gonadotropin for controlled ovarian stimulation in intrauterine insemination (IUI) cycles.Methods: During January-2018 to December-2019 for intending 496 IUI cycles, controlled ovarian stimulation was performed with either clomiphene or letrozole combined with human menopausal gonadotropin (hMG), in two arms: subjects in one arm (Group A) were with clomiphene and hMG in 222 cycles; those in the second arm (Group B) were with letrozole and hMG in 274 cycles. Pregnancy rate and clinical pregnancy rate of both groups were considered as the primary outcomes.Results: Patient characteristics like female age, indications for IUI, type of IUI, endometrial thickness and total motile fraction (TMF) of spermatozoa of male partners were seen similar in both groups. The letrozole-hMG group (Group B) had significantly higher numbers of cycles with single dominant follicle (P=0.01) and human chorionic gonadotropin (hCG) was more frequently used as the ovulation trigger (P=0.03). Pregnancy rate (18.5% vs. 15.3%, P=0.35) and clinical pregnancy rate (18.5% vs. 15.3%, P=0.35) were similar in groups A and B, respectively.Conclusion: Clomiphene citrate and letrozole combined with low dose human menopausal gonadotropin were equally effective for controlled ovarian stimulation in IUI cycles.

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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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