The Impact of Body Weight on Reproductive Outcomes in Poor Ovarian Responders in ICSI Cycles

Study Overview
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Brief Summary
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Induction of ovulation cycle: Gonadotrophines is started on day 2 with HMG(merional, IBSA) ,until the day of HCG administration(choriomon,IBSA10000IU) with starting dose 300 to 450iu. GNRH antagonist (cetrorelix 0,25mg s.c, cetrotide, serono laboratories, Aubonne Switzerland) is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration Ovarian ultrasound scans were performed using a 5.0-9.0 MHZ multi frequency trans vaginal probe (mindrayDP-5)to assess the ovarian response till the mature follicles reach18-20mm when hCG administration 10000 IU is given.Serum E2 level is done on day of HCG trigger. Trans vaginal ultrasound-guided oocyte retrieval is performed 34-36 hours after hCG injection Progesterone vaginal tablets (Prontogest,IBSA) are administrated 400mg twice daily as luteal support from the day of oocytes retrieval. Ultrasound -guided fresh embryo transfer is performed on day 2 or 3 after fertilization. Serum hCG assessment to detect pregnancy is performed at 14 days after embryo transfer .if positive(chemical pregnancy) ,women undergo trans -vaginal ultrasonography 2 weeks after, to confirm fetal pulsations as well as number of gestational sacs (clinical pregnancy). The implantation rate is calculated as the number of viable embryos divided by the number of transferred embryos multiplied by 100

Detailed Description
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Induction of ovulation cycle: Gonadotrophines is started on day 2 with HMG(merional, IBSA) ,until the day of HCG administration(choriomon,IBSA10000IU) with starting dose 300 to 450iu. GNRH antagonist (cetrorelix 0,25mg s.c, cetrotide, serono laboratories, Aubonne Switzerland) is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration Ovarian ultrasound scans were performed using a 5.0-9.0 MHZ multi frequency trans vaginal probe (mindrayDP-5)to assess the ovarian response till the mature follicles reach18-20mm when hCG administration 10000 IU is given.Serum E2 level is done on day of HCG trigger. Trans vaginal ultrasound-guided oocyte retrieval is performed 34-36 hours after hCG injection Progesterone vaginal tablets (Prontogest,IBSA) are administrated 400mg twice daily as luteal support from the day of oocytes retrieval. Ultrasound -guided fresh embryo transfer is performed on day 2 or 3 after fertilization. Serum hCG assessment to detect pregnancy is performed at 14 days after embryo transfer .if positive(chemical pregnancy) ,women undergo trans -vaginal ultrasonography 2 weeks after, to confirm fetal pulsations as well as number of gestational sacs (clinical pregnancy). The implantation rate is calculated as the number of viable embryos divided by the number of transferred embryos multiplied by 100

Official Title
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The Impact of Overweight and Obesity on Reproductive Outcomes in Poor Ovarian Responders in ICSI Cycles

Conditions
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Invitro Fertilization

Intervention / Treatment
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* Drug: Gonadotropins
* Drug: GNRH antagonist
* Drug: Human chorionic gonadotropin Chorimon
* Drug: Natural progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 4- Poor responder according to ESHRE consensus; in which at least 2 of the following should be present: Advanced maternal age (≥ 40 years old) or any other risk factor A previous poor ovarian response (cycles cancelled or ≤ 3 oocytes with a conventional protocol)An abnormal ovarian reserve test (ORT); antral follicle count (AFC) < 5-7 follicles or anti-mullerian hormone (AMH) ≤0.5- 1.1 ng/ml In the absence of advanced maternal age or abnormal ORT, two previous episodes of poor ovarian response after maximal stimulation patients are also considered poor responders according to ESHRE consensus. Presence and Adequate visualization of both ovaries Uterine cavity within normal anatomy assessed with HSG, hysteroscopy and TVUS Exclusion Criteria: Any factor which may affect reproductive outcome other than that the patient is a poor responder will be excluded from the study, like: Severe male factor . Uterine factor (eg: fibroid, polyp, Ashermann, .. etc) Immunological disorder (eg: SLE, APS, … etc) Thyroid or adrenal dysfunction Neoplasia (especially: hypothalamic, pit, ovarian) Women diagnosed with PCOS according to Rotterdam criteria Hydrosalpinx that hasn't been surgically removed or ligated. Untreated hyperprolactinemia Abnormal bleeding disorder Hepatic or renal dysfunction Hypersenstivity to study medication ( GNRH antagonist) Need to take medication that can influence ovarian stimulation Endometriosis grade 3 or 4 Ovarian cyst> 10 cm.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 44 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Normal weight<br>18.5- 24.9 kg/m2 | Drug: Gonadotropins<br>* 1) Gonadotrophines is started on day 2 with HMG(merional, IBSA) ,until the day of HCG administration<br>* Other names: Human menopausal gonadotropin;Drug: GNRH antagonist<br>* cetrorelix 0,25mg s.c is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration<br>* Other names: cetrorelix;Drug: Human chorionic gonadotropin Chorimon<br>* 10000 IU of HCG are given intramuscular when 2 or more mature follicles reach 18 - 20 mm<br>* Other names: HCG;Drug: Natural progesterone<br>* 400 mg vaginal tablets twice daily from the day of ovum pick up till HCG tesing<br>* Other names: prontogest;|
| Active Comparator: Overweight<br>BMI 25-29.9 kg/m2 | Drug: Gonadotropins<br>* 1) Gonadotrophines is started on day 2 with HMG(merional, IBSA) ,until the day of HCG administration<br>* Other names: Human menopausal gonadotropin;Drug: GNRH antagonist<br>* cetrorelix 0,25mg s.c is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration<br>* Other names: cetrorelix;Drug: Human chorionic gonadotropin Chorimon<br>* 10000 IU of HCG are given intramuscular when 2 or more mature follicles reach 18 - 20 mm<br>* Other names: HCG;Drug: Natural progesterone<br>* 400 mg vaginal tablets twice daily from the day of ovum pick up till HCG tesing<br>* Other names: prontogest;|
| Active Comparator: Obese<br>BMI ≥ 30 kg/m2 | Drug: Gonadotropins<br>* 1) Gonadotrophines is started on day 2 with HMG(merional, IBSA) ,until the day of HCG administration<br>* Other names: Human menopausal gonadotropin;Drug: GNRH antagonist<br>* cetrorelix 0,25mg s.c is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration<br>* Other names: cetrorelix;Drug: Human chorionic gonadotropin Chorimon<br>* 10000 IU of HCG are given intramuscular when 2 or more mature follicles reach 18 - 20 mm<br>* Other names: HCG;Drug: Natural progesterone<br>* 400 mg vaginal tablets twice daily from the day of ovum pick up till HCG tesing<br>* Other names: prontogest;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical pregnancy rate | appearance of intrauterine gestational sac by transvaginal ultrasound | 4 weeks after HCG triggering |