Study on Influence of Leutinizing Hormone (LH) on Oocyte Maturity (LH/M2-Oocyte)

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)?

1. Leutinizing hormone (LH) has been demonstrated to exert variable physiological actions during menstrual cycle at appropriate plasma levels'
2. 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).
3. 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.
4. 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.

Study Overview

• Status: Unknown
• Conditions: Infertility
• Intervention / Treatment: Drug: Cetrorelix; Drug: Luprolide Acetate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Gujarat
    • Anand, Gujarat, India
      • Recruiting
      • Sat Kaival Hospital Pvt. Ltd.
      • Contact: Nayana Patel, MD
      • Principal Investigator: Nayana Patel;, MD
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India
      • Recruiting
      • Disha Fertility & Surgical Hospital
      • Contact: Asha Baxi, MD, FRCOG
      • Principal Investigator: Asha Baxi, MD, FRCOG
  • Maharashtra
    • Mumbai, Maharashtra, India
      • Recruiting
      • Southern Cross Fertility Center
      • Contact: Faram Irani, MD
      • Principal Investigator: Faram Irani, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study subjects desiring pregnancy; 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; 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; Other Names: Cetrotide
Other: Control subjects desiring pregnancy; 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; Women in the control arm would receive Luprolide acetate 1 mg/day by subcutaneous injection; Other Names: Lupron

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Southern Cross Fertility Centre
• Collaborators: Disha Fertility and Surgical Centre,Indore,India
• Investigators: Study Director: M R Bharucha, PhD, Sat Kaival Pvt. Ltd, Anand, Gujarat; Principal Investigator: Nayana Patel, MD, Sat Kaival Hospital Pvt. Ltd, Anand, Guajarat; Principal Investigator: Faram Irani, MD, Southern Cross Fertility Center, Mumbai, India; Principal Investigator: Asha Baxi, MD, FRCOG, Disha Fertility & Surgical Hospital, Indore, India

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Anticipated): September 1, 2012
• Study Completion (Anticipated): November 1, 2012

Study Registration Dates

• First Submitted: April 27, 2012
• First Submitted That Met QC Criteria: May 8, 2012
• First Posted (Estimate): May 10, 2012

Study Record Updates

• Last Update Posted (Estimate): May 25, 2012
• Last Update Submitted That Met QC Criteria: May 24, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: ICSI; IVF-ET; Cetrorelix; Gonadotrophins; Leuprolide acetate; rLH; rFSH
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Cetrorelix
• Other Study ID Numbers: MB/LH-M2/OM/2011