Dual Trigger Versus GnRHa Trigger Combined With Luteal HCG Administration

Study Overview
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Brief Summary
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Comparing the reproductive outcomes of intracytoplasmic sperm injection (ICSI) cycles in women at risk of ovarian hyperstimulation syndrome (OHSS) subjected to gonadotropin releasing hormone (GnRH) antagonist protocol followed by trigger with concomitant GnRH agonist (GnRHa) and low-dose human chorionic gonadotropin (HCG) administration (dual trigger), GnRHa trigger with single luteal low-dose HCG or GnRHa trigger with multiple luteal low-doses HCG

Detailed Description
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The GnRH antagonist fixed protocol will be used for controlled ovarian hyperstimulation (COH). Transvaginal sonography (TVS) scan will be performed regularly for monitoring of the follicular growth (folliculometry). When there will be at least 3 leading follicles > 18 mm in diameter, women will be randomized into 3 groups; group A (dual trigger group), group B (single low-dose HCG group) and group C (multiple low-doses HCG group). In group A, final oocyte maturation will be triggered by dual administration of 0.2 mg of GnRHa preparation (Triptorelin) SC and 1500 IU of HCG preparation IM. In group B, final oocyte maturation will be triggered by administration of 0.2 mg Triptorelin SC then a single IM bolus of 1500 IU HCG will by administered 35-37 hours after GnRHa trigger (1 hour after oocyte retrieval). In group C, final oocyte maturation will be triggered by administration of 0.2 mg Triptorelin SC then 3 IM boluses of 500 IU HCG will be administered day 1, day 4 and day 7 after oocyte retrieval. In all women, oocyte retrieval will be performed 34-36 hours after trigger and endometrial preparation for embryo transfer (ET) will be started on the day of oocyte retrieval by giving 400 mg vaginal natural progesterone supplement once daily plus 4 mg oral estradiol valerate once daily.

Official Title
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Dual Trigger Versus Gonadotropin Releasing Hormone Agonist Trigger Combined With Luteal Human Chorionic Gonadotropin Administration

Conditions
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Infertility

Intervention / Treatment
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* Drug: GnRHa and HCG
* Drug: GnRHa then HCG (single low-dose)
* Drug: GnRHa then HCG (multiple low-doses)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women subjected to ICSI through controlled ovarian hyperstimulation (COH) with pituitary downregulation by GnRH antagonist. Presence of risk for development of OHSS: 1) previous moderate or severe OHSS; 2) PCOS or polycystic ovary on ultrasound scan; 3) antral follicle count (AFC) > 14 in both ovaries; 4) basal serum AMH level > 3.36 ng/ml; 5) > 14 follicles with diameter of ≥ 11 mm on the day of triggering of oocyte maturation; 6) E2 level > 3000 pg/ml on the day of triggering of oocyte maturation. Exclusion Criteria: Age < 20 years or > 35 years. BMI < 19 kg/m2 or > 35 kg/m2. Moderate or severe endometriosis. Hydrosalpinx. Uterine abnormalities or myoma. Previous uterine surgery. Use of alternative techniques to minimize the risk of OHSS.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dual trigger group<br>Trigger with concomitant GnRHa and HCG (single low-dose) administration | Drug: GnRHa and HCG<br>* Final oocyte maturation will be triggered by dual administration of 0.2 mg of GnRHa preparation (Triptorelin) SC and 1500 IU of HCG preparation IM<br>* Other names: Decapeptyl and Pregnyl;|
| Active Comparator: Single low-dose HCG group<br>Trigger with GnRHa then HCG (single low-dose) administration in luteal phase | Drug: GnRHa then HCG (single low-dose)<br>* Final oocyte maturation will be triggered by administration of 0.2 mg Triptorelin SC then a single IM bolus of 1500 IU HCG will be administered 35-37 hours after GnRHa trigger (1 hour after oocyte retrieval)<br>* Other names: Decapeptyl then Pregnyl;|
| Active Comparator: Multiple low-doses HCG group<br>Trigger with GnRHa then HCG (multiple low-doses) administration in luteal phase | Drug: GnRHa then HCG (multiple low-doses)<br>* Final oocyte maturation will be triggered by administration of 0.2 mg Triptorelin SC then 3 IM boluses of 500 IU HCG will be administered day 1, day 4 and day 7 after oocyte retrieval<br>* Other names: Decapeptyl then Pregnyl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Number of clinical pregnancies (defined as presence of at least one intrauterine gestational sac with fetal pole and cardiac activity on TVS scan at 4-6 weeks after the ET) divided by the number of ET procedures | 6 weeks after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oocyte maturation rate | Number of mature oocytes divided by the number of retrieved oocytes | On day of oocyte retrieval | 
| Incidence of early OHSS | Incidence of OHSS within 9 days of final triggering of oocyte maturation | Within 9 days of final triggering of oocyte maturation | 
| Implantation rate | Number of gestational sacs on TVS scan at 4-6 weeks after ET divided by the number of transferred embryos | 6 weeks after embryo transfer | 
| Miscarriage rate | Number of first trimester miscarriages (before 12 weeks gestational age) divided by the number of clinical pregnancies | 12 weeks gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GnRHa trigger, Luteal phase support, OHSS