Stimulated Versus Un-stimulated Intrauterine Insemination Cycles in Couples With Mild Male Factor Infertility

Stimulated Versus Un-stimulated Intrauterine Insemination Cycles in Couples With Mild Male Factor Infertility: A Randomized Controlled Trial

Four hundred and fifty women with mild male factor infertility 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

Study Overview

• Status: Unknown
• Conditions: Subfertility
• Intervention / Treatment: Drug: Merional; Drug: Choriomon; Procedure: IUI; Device: Shepherd catheter; Procedure: Ovulation detection

Detailed Description

Mild male factor infertility is defined as: Two or more semen analyses that have one or more variables which fall below the 5th centile as defined by the World Health Organization, and where the effect on the chance of pregnancy occurring naturally through vaginal intercourse within a period of 24 months would then be similar to people with unexplained infertility or mild endometriosis. 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 the management of mild male factor infertility.

The study will be conducted in Cairo university hospitals and BeniSuef University hospitals All patients with mild male factor infertility 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 mild male factor infertility 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 3nd 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.

• Study Type: Interventional
• Enrollment (Anticipated): 450
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • BeniSuef, Egypt
    • Recruiting
    • BeniSuef University hospitals
    • Principal Investigator: Nesreen Shehata, Md
  • Cairo, Egypt
    • Recruiting
    • Cairo University Hospitals
    • Contact: AbdelGany Hassan, MRCOG, MD; Phone Number: 002 01017801604; Email: abdelgany2@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Mild male factor infertility defined as meaning two or more semen analyses that have one or more variables which fall below the 5th centile as defined by the World Health Organization, and where the effect on the chance of pregnancy occurring naturally through vaginal intercourse within a period of 24 months would then be similar to people with unexplained infertility or mild endometriosis.

Exclusion Criteria:

• Known allergy to FSH
• Other factors of infertility.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: stimulated intrauterine insemination (IUI); 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; 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.; Drug: Choriomon; 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.; Procedure: IUI; Semen will be processed and drawn into a shepherd catheter attached to a 1 mL syringe and injected into the uterus; Device: Shepherd catheter; Processes semen will be drawn into a shepherd catheter attached to a 1 mL syringe and injected into the uterus
Active Comparator: Unstimulated IUI; 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; Semen will be processed and drawn into a shepherd catheter attached to a 1 mL syringe and injected into the uterus; Device: Shepherd catheter; Processes semen will be drawn into a shepherd catheter attached to a 1 mL syringe and injected into the uterus; Procedure: Ovulation detection; 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
Active Comparator: Control group; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ongoing pregnancy rate	12 weeks after IUI or timed sexual intercourse

Collaborators and Investigators

• Sponsor: Cairo University

Publications and helpful links

General Publications

• Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010 May-Jun;16(3):231-45. doi: 10.1093/humupd/dmp048. Epub 2009 Nov 24.
• Quintero RB, Urban R, Lathi RB, Westphal LM, Dahan MH. A comparison of letrozole to gonadotropins for ovulation induction, in subjects who failed to conceive with clomiphene citrate. Fertil Steril. 2007 Oct;88(4):879-85. doi: 10.1016/j.fertnstert.2006.11.166.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: June 9, 2015
• First Submitted That Met QC Criteria: June 9, 2015
• First Posted (Estimate): June 11, 2015

Study Record Updates

• Last Update Posted (Actual): January 3, 2018
• Last Update Submitted That Met QC Criteria: December 29, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: sub 12