Study on Influence of Leutinizing Hormone (LH) on Oocyte Maturity

Study Overview
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Brief Summary
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Leutinizing hormone (LH) has been demonstrated to exert variable physiological actions during menstrual cycle at appropriate plasma levels' In early follicular phase,in the requisite range,LH is known to contribute to maturation of oocyte during transition phase from metaphase-1(M1) to metaphase-2 (M2). If during this transition, appropriate level of LH can be maintained either through the use of gonadotropin releasing hormone (GnRH) antagonist if found excessive or supplementation with exogenous LH, if found deficient, maturation process can be enhanced. Further maintenance of suitable combination of recombinant follicle stimulating hormone (rFSH) + rLH can help in realizing higher yield of mature M2 oocytes,with higher probability of establishing clinical pregnancy.

Detailed Description
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The study is planned to assess whether maintenance of levels of LH through the use of GnRH antagonist would contribute to obtaining mature M2 oocytes so that maximum number of good quality embryo's with potential to implant is obtained. The mature oocytes would be subjected to either standard in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) depending on the status of the male factor. The objective would be to obtain good quality embryo's with implantation potential for fresh embryo transfer and/or subsequent frozen thaw embryo transfer. In both these events, the secondary outcome measures would be establishment of clinical pregnancy by transvaginal ultrasound performed 6 weeks after embryo transfer.

Official Title
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Is it Possible to Obtain Higher Yield of Mature M2 Oocytes by Establishing Appropriate Levels of LH During Controlled Ovarian Hyperstimulation (COH) in Antagonist Cycles for In-vitro Fertilization-embryo Transfer (IVF-ET)/ Intracytoplasmic Sperm Injection (ICSI)?

Conditions
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Infertility

Intervention / Treatment
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* Drug: Cetrorelix
* Drug: Luprolide Acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18-40 years Primary or secondary infertility Desire to achieve pregnancy Basal FSH <12 mIU/ML Moderate to good ovarian reserve (antimullerian hormone (AMH) >1ng/ml, and/ or antral follicle count (AFC)>8 between both ovaries) Informed written consent from both partners BMI <35 kg/mtr.sq. No genetic abnormality Exclusion Criteria: Hormonal preparation taken within 3 month prior to recruitment Women with previous poor response to gonadotrophins History of previous 3 or more miscarriages Women with uncorrected tubal/uterine pathology Women opting for assisted procedures like embryo hatching etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study subjects desiring pregnancy<br>Study subjects to be treated with rFSH, rLH throughout controlled ovarian hyperstimulation (COH) in appropriate dosages,considering age, body mass index (BMI), ovarian reserve, etc. and GnRH antagonist, cetrorelix in 0.25 mg/d when needed till the desired follicular maturity and the minimum required number of follicles are achieved. INTRVENTIONS - Monitoring at regular intervals by transvaginal ultrasound and hormonal studies.Once pregnancy established by beta-human chorionic gonadotropin (hCG) and ultrasound will be supported by intervention of adequate luteal support by estrogen (E) + progesterone (P) for 12 weeks of gestation. | Drug: Cetrorelix<br>* Cetrorelix 0.25 mg/d would be administered by subcutaneous injection to women when the plasma LH is higher (>4.5 mIU/ml) in the study arm<br>* Other names: Cetrotide;|
| Other: Control subjects desiring pregnancy<br>Control subjects selected in randomized way,desiring pregnancy will be treated with gonadotrophins, rFSH and rLH in appropriate dosages considering age, BMI, ovarian reserve, etc. after standard downregulation with GnRH agonist, Leuprolide acetate, 1 mg/d under established 'Long Luteal Suppression Protocol' from the previous cycle. INTERVENTIONS - Monitoring of response to treatment by hormonal study and sonography evaluation at regular intervals during COH till adequate number of mature follicles of minimum 18 mm mean diameter is achieved, to be followed by hCG trigger and ovum pick-up (OPU) and embryo transfer (ET). Chemical pregnancy by beta-hCG would be confirmed 14 days post-ET. Clinical pregnancy would be confirmed by sonography 6 weeks after ET (visibility of yolk sac and fetal heart-beat). Pregnancy support by E+P for 12 weeks would be provided. | Drug: Luprolide Acetate<br>* Women in the control arm would receive Luprolide acetate 1 mg/day by subcutaneous injection<br>* Other names: Lupron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of mature oocytes immediately after oocyte recovery | Number of mature oocytes would be measured immediately after the oocyte recovery | Women would be followed every 2 weeks upto 6 weeks after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy | Diagnosed by transvaginal ultrasound.Appearance of yolk sac with fetal heart beat at 6 weeks of gestation. | Women would be followed every 2 weeks upto 6 weeks after embryo transfer | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF-ET, ICSI, Gonadotrophins, rFSH, rLH, Cetrorelix, Leuprolide acetate