Stimulated Versus Un-stimulated Intrauterine Insemination Cycles in Women With Endometriosis

Study Overview
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Brief Summary
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Four hundred and fifty women with endometriosis will be divided into 3 equal groups using computer generated random numbers: Group 1 will have up to 4 stimulated intrauterine insemination (IUI) cycles, group 2 will have up to 4 unstimulated cycles, women who do not become pregnant after the 4 cycles in groups 1 and 2 will be advised to have regular intercourse at the expected time of ovulation. Group 3 will be the control group will be advised to have regular sexual intercourse at the time of ovulation for 4 months

Detailed Description
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Endometriosis is defined as the presence of endometrial like tissue (glands or stroma) outside the uterus, which induces a chronic inflammatory reaction. The exact prevalence of endometriosis is unknown but estimated to range from 2 to 10% in women of childbearing age. Its prevalence rises up to 50% in women with infertility. In subfertile patients with moderate-to-severe endometriosis, the anatomy of the pelvic cavity can be disturbed resulting in impaired ovum retrieval or diminished patency of the Fallopian tubes, making IVF the first choice of fertility treatment. However, in patients with surgically treated endometriosis in which normal functioning ovum retrieval and patency of at least one Fallopian tube has been established, intrauterine insemination (IUI) can be provided prior to IVF. The application of ovarian stimulation in IUI is advocated, even if the woman has ovulatory cycles, to improve the pregnancy rates with IUI. However, the application of ovarian stimulation has two main drawbacks: The increased chances of a multiple pregnancy and ovarian hyperstimulation syndrome. To avoid these complications unstimulated IUI cycles have been investigated. The objective of the study is to evaluate the role of stimulated and unstimulated IUI cycles in women with endometriosis. The study will be conducted in Cairo university hospitals and BeniSuef University hospitals All patients with laparoscopic documented endometriosis attending both sites will be invited to participate in the study. The study will be explained and only couples who sign written consents will be included in the study. Four hundred and fifty women with endometriosis will be divided into 3 equal groups using computer generated random numbers: Group 1 will have up to 4 stimulated IUI cycles, group 2 will have up to 4 unstimulated cycles, women who do not become pregnant after the 4 cycles in groups 1 and 2 will be advised to have regular intercourse at the expected time of ovulation. Group 3 will be the control group will be advised to have regular sexual intercourse at the time of ovulation for 6 months On the 3rd day of menstruation group 1 will have a vaginal ultrasound and will receive daily intramuscular 150 IU of human menopausal gonadotropins (hMG, Merional ®, IBSA, Lugano, Switzerland) starting from the 3rd day of menstruation. On day 8 the ultrasound will be repeated and serum E2 will be measured, hMG dose will be adjusted and continued and the frequency of ultrasound scans will be individualized. HMG will be stopped when at least 2 follicles measuring 18 mm are associated with serum E2 of 500-3000 Pg/mL, this was followed by the administration of 10000 IU of human chorionic gonadotropin (hCG; Choriomon®, IBSA) Women in group 2 will be asked to test their morning urine specimen for luteinizing hormone daily starting 4 days before the expected day of ovulation. This will be done using a qualitative kit. Intrauterine insemination will be performed on the day after the surge in urinary excretion of luteinizing hormone. Women in group 3 will be asked to test their urine for luteinizing hormone by the same method as group 2. They will be asked to have an intercourse on the day after the surge in urinary excretion of luteinizing hormone and this will be repeated for 12 months. Semen specimens for groups 1 and 2 will be evaluated and prepared for IUI within one hour after collection. Semen will be diluted 1:2 (vol/vol) with HEPES-buffered Ham's F10 medium containing 1.5 percent serum albumin. After centrifugation for 10 minutes, the pellets will be re-suspended and combined in 3 ml of the medium. The sperm suspension will be centrifuged for 10 minutes, and the pellet was resuspended in 0.35 ml of medium. Approximately 0.05 ml will be used to determine the concentration and motility of sperms. The remaining sample will be drawn into a shepherd catheter attached to a 1 mL syringe and injected into the uterus. The procedure will be repeated for up to 4 months in groups 1 and 2, if pregnancy does not occur. Women who do not conceive after the 4 trials will be asked to check their urine for luteinizing hormone using the ovulation detection kits and have an intercourse on the day following the luteinizing hormone surge. This will be repeated for 8 months. The pregnancy rates of the 3 groups will be compared after the 4 months and after one year.

Official Title
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Stimulated Versus Un-stimulated Intrauterine Insemination Cycles in Women With Endometriosis: A Randomized Controlled Trial

Conditions
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Subfertility

Intervention / Treatment
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* Drug: Merional
* Procedure: IUI
* Drug: Choriomon
* Device: shepherd catheter
* Procedure: Ovulation detection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Endometriosis Exclusion Criteria: Known allergy to FSH Diabetes Hypertension known cardiac, renal or liver disease

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stimulated IUI<br>On the 3rd day of menstruation women in group 1 will have a vaginal ultrasound and will receive daily intramuscular 150 IU of human menopausal gonadotropins starting from the 3rd day of menstruation. On day 8 the ultrasound will be repeated and serum E2 will be measured, hMG dose will be adjusted and continued and the frequency of ultrasound scans will be individualized. HMG will be stopped when at least 2 follicles measuring 18 mm are associated with serum E2 of 500-3000 Pg/mL, this was followed by the administration of 10000 IU of human chorionic gonadotropin | Drug: Merional<br>* On the 3rd day of menstruation women will have a vaginal ultrasound and will receive daily intramuscular 150 IU of human menopausal gonadotropins (hMG, Merional ®, IBSA, Lugano, Switzerland) starting from the 3nd day of menstruation.<br>Procedure: IUI<br>* Semen will be processed and drawn into a shepherd catheter attached to a 1 mL syringe and injected into the uterus<br>Drug: Choriomon<br>* Administration of 10000 IU of human chorionic gonadotropin (hCG; Choriomon®, IBSA) when at least 2 follicles measuring 18 mm are observed during vaginal ultrasound and is associated with serum E2 of 500-3000 Pg/mL<br>Device: shepherd catheter<br> <br> |
| Active Comparator: Unstimulated IUI<br>Women in group 2 will be asked to test their morning urine specimen for luteinizing hormone daily starting 4 days before the expected day of ovulation. This will be done using a qualitative kit. IUI will be performed on the day after the surge in urinary excretion of luteinizing hormone. | Procedure: IUI<br>* Semen will be processed and drawn into a shepherd catheter attached to a 1 mL syringe and injected into the uterus<br>Device: shepherd catheter<br> <br> Procedure: Ovulation detection<br>* Women will be asked to test their morning urine specimen for luteinizing hormone daily starting 4 days before the expected day of ovulation. This will be done using a qualitative kit<br>|
| Active Comparator: Control group<br>Women will be asked to test their urine for luteinizing hormone by the same method as group 2. They will be asked to have an intercourse on the day after the surge in urinary excretion of luteinizing hormone and this will be repeated for 12 months. | Procedure: Ovulation detection<br>* Women will be asked to test their morning urine specimen for luteinizing hormone daily starting 4 days before the expected day of ovulation. This will be done using a qualitative kit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy | confirmation of an ongoing pregnancy by detecting fetal heart beat during abdominal ultrasound examination 12 weeks after IUI or timed sexual intercourse. | 12 weeks after IUI or timed sexual intercourse |