Clomiphene Citrate, Estradiol and Sildenafil for Induction of Ovulation in Unexplained Infertility

NCT ID: NCT03755037

Last Updated: 2018-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2018-04-30

Brief Summary

Diagnosis of unexplained infertility is made after the recommended testing fails to reveal any abnormality. The treatment for unexplained infertility is empiric because it does not address a specific defect or functional impairment. The principal treatments for unexplained infertility include expectant observation with timed intercourse and lifestyle changes, clomiphene citrate and intrauterine insemination (IUI), controlled ovarian hyperstimulation (COH) with IUI, and IVF).

Detailed Description

Clomiphene citrate has been widely used alone, and in combination with intrauterine insemination (IUI), for treatment of unexplained subfertility, The mechanism of action is based on its mixed estrogenic and antiestrogenic properties. Clomiphene is frequently used to treat unexplained female infertility by inducing multifollicular response and correcting potential subtle ovulatory dysfunction .,)The American Society for Reproductive Medicine,2003).

The use of clomiphene citrate decreases the uterine blood flow during the early luteal phase, a periimplantation stage., )The American College of Obstetricians and Gynecologists,1995).

Although ovulation is found in 80% of women with a cumulative effect in 6-8 months, the pregnancy rate can still be very low in these women . The possible causes are the anti-estrogenic effects of CC at the endometrium and cervical mucus level . The endometrial effect is without doubt one of the most important handicaps in infertility treatment. The pregnancy rate can be very low, especially if the endometrial thickness (ET) is <6-8 mm ., )J Turk Ger Gynecol Assoc. ,2012).

Ethinyl E2 reverse the deleterious effect of CC on endometrial development during the follicular phase. Endometrial thickness was dependent on peak E2 concentrations in serum.,(Richard P. Dickey, et.al.,2003).

Sildenafil citrate could lead to an improvement in uterine blood flow and, in conjunction with estrogen, led to the estrogen-induced proliferation of the endometrial lining .

Sildenafil citrate enhances uterine blood flow and increases endometrial thickening . The achieved implantation depends on the blastocyst's ability to infiltrate the endometrium and develop a sustaining blood supply, which requires the following genes to produce the necessary proteins for digesting the endometrial cellular matrix, to regulate cell growth, and to induce angiogenesis (Razieh Dehghani Firouzabadi,et.al.,2013).

Conditions

Female Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Estradiol and cc

Group 1 received estradiol, cc and placebo simillar to sildenafil for induction of ovulation.

CC 50 mg (clomid) orally twice daily from 3rd day to 7th day of menstrual cycle of the patient then ethinyl estradiol 0.05mg orally twice daily on the 8th day of same cycle till 11th day.

Group Type: ACTIVE_COMPARATOR

Clomid, Respatio and Ethinyl estradiol

Intervention Type: DRUG

Drugs were received during the menstrual cycle.

Sildenafil and cc

Group 2 received CC 50 mg (clomid) orally twice daily from 3rd day to 7th day of menstrual cycle of the patient, sildenafil citrate (Respatio) 20 mg tab orally 3 times daily from8th day of same cycle till 11th day and placebo simillar to estradiol.

Group Type: ACTIVE_COMPARATOR

Clomid, Respatio and Ethinyl estradiol

Intervention Type: DRUG

Drugs were received during the menstrual cycle.

Placebo and cc

Group 3 received cc and placebo similar to sildenafil and placebo similar to estradiol with the same doses.

Group Type: PLACEBO_COMPARATOR

Clomid, Respatio and Ethinyl estradiol

Intervention Type: DRUG

Drugs were received during the menstrual cycle.

Interventions

Clomid, Respatio and Ethinyl estradiol

Drugs were received during the menstrual cycle.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women whose infertility tests were normal then diagnosed as unexplained infertility.

Exclusion Criteria

• Any cause of infertility male factor, tubal or ovarian.
• Chronic illness as cardiac or renal disease
• Any contraindication for used drugs

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Beni-Suef University

OTHER

Sponsor Role: collaborator

Nesreen Abdel Fattah Abdullah Shehata

OTHER

Sponsor Role: lead

Responsible Party

Nesreen Abdel Fattah Abdullah Shehata

Assistant professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Nesreen Abd El Fattah Abd Allah

Cairo, , Egypt

Countries

Egypt

References

1. Alexander Quaas, MD, Ph .D .,and Anuja Dokras, MD . diagnosis and treatment of unexplainrd infertilityRev Obstet Gynecol. 2008 Spring; 1(2): 69-76 2. J Turk Ger Gynecol Assoc.: The effect of administering estrogen to clomiphene citrate stimulated cycles on endometrial thickness and pregnancy rates in unexplained infertility. (2012) . Sep 1;13(3):157-61. 3. Paulus WE, Strehler E, Zhang M, Jelinkova L,El-Danasouri I and Sterzik K. : Benefit of sildenafil citrate in assisted reproductivetherapy. Fertil Steri 2002 Apr;77(4):846-7. 4. Razieh Dehghani Firouzabadi, M.D., Robab Davar, M.D., Farzaneh Hojjat, M.D., and Mohamad Mahdavi, M.D. :effect of sildenafil on endomeerial preparation and outcome of frozen_thawed embryo transfer cycles(. Iran J Reprod Med. 2013 Feb; 11(2): 151-158. 5. Richard P. Dickey, M.D., Ph.D.,):clomiphene citrate for woman with unexplained infertility . pp 261-271 13 May 2015 6. The American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women:. Fertil Steril . Fertil Steril. 2013 Aug;100(2):341-8. doi: 10.1016/j.fertnstert.2013.05.033. Epub 2013 Jun 27.

Reference Type: BACKGROUND

Other Identifiers

Beni-Suef 16

Identifier Type: -

Identifier Source: org_study_id