Endometrial Receptivity After GnRH Agonist Triggering

Study Overview
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Brief Summary
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Conventional luteal phase support after human chorionic gonadotrophin (hCG) triggering in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) provides adequate pregnancy rates and live birth rates, but Ovarian hyperstimulation syndrome (OHSS) still occurs in 1-3% of the patients. If gonadotropin-releasing hormone agonist (GnRHa) are used instead of hCG, OHSS does not occur, but clinical results are somehow diminished. By testing different luteal support protocols on women undergoing GnRHa triggering, the investigators aim to find out which protocol resembles the most the gene expression profile observed after hCG triggering and conventional luteal phase support, in order to choose it as the most adequate in terms of endometrium receptivity and safety (OHSS incidence).

Official Title
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Endometrial Receptivity After GnRH Agonist Triggering From Final Oocyte Maturation

Conditions
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Ovarian Hyperstimulation Syndrome

Intervention / Treatment
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* Drug: hCG
* Drug: triptorelin
* Drug: Triptorelin, estradiol valerate, micronized vaginal progesterone
* Drug: triptorelin, hCG
* Drug: triptorelin, hCG
* Drug: triptorelin, recombinant LH


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Healthy oocyte donor women Aged 18-35 years With a menstrual cycle length of 26-35 days Normal ultrasound scan of uterus and ovaries Normal basal hormones No contraindication for controlled ovarian stimulation (COS) Willing to participate in the study and providing written informed consent. Exclusion Criteria: Subjects with current or previous history of an endocrine abnormality Subjects with an abnormal outcome of blood biochemistry or hematology Subjects with an abnormal cervical smear Subjects with a chronic disease Subjects with any relevant ovarian-, tubal- or uterine-pathology that could interfere with the COS treatment Pregnancy Subjects who had a previous history of ovarian hyperresponse or ovarian hyperstimulation syndrome (OHSS), polycystic ovary syndrome (PCOS) or a basal antral follicle count (AFC) of more than 20 on ultrasound (11 mm, both ovaries combined) . Previous low ovarian response to FSH or hMG treatment (i.e. cycle cancelled due to insufficient ovarian response or less than 6 oocytes obtained). A history of recurrent miscarriage, Smoking more than 10 cigarettes per day. Not willing to comply with study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: hCG<br> | Drug: hCG<br>* single shot of 6500 IU hCG s.c. at the time of triggering<br>|
| Experimental: Triptorelin 0.2mg s.c.<br> | Drug: triptorelin<br>* single shot of 0.2mg triptorelin s.c. at the time of triggering<br>|
| Experimental: 0.2mg triptorelin plus estradiol/progesterone<br> | Drug: Triptorelin, estradiol valerate, micronized vaginal progesterone<br>* 4mg of estradiol valerate per os plus 400mg micronized vaginal progesterone daily starting the day after OPU<br>|
| Experimental: 0.2mg tripoterlin plus single bolus hCG 1500 IU<br> | Drug: triptorelin, hCG<br>* single shot of 1500 IU hCG s.c. the day of OPU plus 4mg of estradiol valerate per os plus 400mg micronized vaginal progesterone daily starting the day after OPU<br>|
| Experimental: 0.2mg tripoterlin plus multiple boluses hCG 500 IU<br> | Drug: triptorelin, hCG<br>* Multiple doses of 500 IU hCG (OPU, +4 and +7) and 4mg of estradiol valerate per os plus 400mg micronized vaginal progesterone daily starting the day after OPU<br>|
| Experimental: 0.2mg tripoterlin plus multiple doses recLH<br> | Drug: triptorelin, recombinant LH<br>* 300 IU recombinant LH every 48h and 4mg of estradiol valerate per os plus 400mg micronized vaginal progesterone daily starting the day after OPU<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endometrial receptivity gene expression profile |  | participants will be followed for the duration of the cycle, an expected average of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of moderate/severe OHSS in all different treatment group | Mild OHSS Grade 1, abdominal distension and discomfort Grade 2, features of grade 1 plus nausea, vomiting and/or diarrhea; ovaries are enlarged from 5 to 12 cm Moderate OHSS Grade 3, features of mild OHSS plus ultrasonic evidence of ascites Severe OHSS Grade 4, features of moderate OHSS plus evidence of ascites and/or hydrothorax and breathing difficulties Grade 5, all of the above, plus change in the blood volume, increased blood viscosity due to hemoconcentration, coagulation abnormality, and diminished renal perfusion and function | participants will be followed for the duration of the cycle, an expected average of 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OHSS, endometrial receptivity, gene arrays, agonist triggering, Endometrial gene expression