Clinical trial NCT02802865: Combined Letrozole and Clomid in Women With Infertility and PCOS
Official title: Combined Letrozole and Clomid in Polycystic Ovary Syndrome: a Randomized Control Trial of Combination of Letrozole and Clomiphene Citrate or Letrozole Alone for the Treatment of Infertility in Women With Polycystic Ovary Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Polycystic Ovary Syndrome
Infertility
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2016-06-16
Enrollment: 70
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the addition of clomid to letrozole for the treatment of infertility in women with polycystic ovary syndrome. Half of the participants will receive letrozole and clomid in combination, while the other half will receive letrozole alone.

Detailed description: Letrozole and Clomid are both used for ovulation induction, but they have different mechanisms of action. Letrozole has been shown to be superior to clomid in achieving live birth rates in women with infertility and polycystic ovary syndrome. However, the combination of these medications has not been studied. This is a pilot study to evaluate if the combination treatment has improved efficacy as measured by ovulation rate.

This is a randomized controlled trial of letrozole versus letrozole and clomiphene citrate (CC) for one menstrual cycle. Women will be randomized in a 1:1 ratio to receive letrozole 2.5 mg or combination of letrozole 2.5 mg and clomiphene 50 mg for 5 days on days 3-7 of menstrual cycle. The women and their partners will be instructed to have regular intercourse with the intent to conceive during the cycle. Patients will have an transvaginal ultrasound mid cycle and to evaluate number of follicles (\>15 mm), follicle size, endometrial thickness and pattern. Patients will have mid- luteal phase progesterone level drawn to evaluate ovulation. Side effect profile will also be monitored.

Eligibility criteria: Inclusion Criteria:

1. Willing to comply with all study procedures and be available for the duration of the study
2. Diagnosis of infertility: Inability of couple to achieve successful pregnancy after 12 months of regular timed unprotected intercourse in women less than 35 years of age; and after 6 months of regular intercourse without use of contraception in women 35 years and older
3. Diagnosis of polycystic ovary syndrome based on Revised Rotterdam criteria
4. Ability to have regular intercourse during the ovulation induction phase of the study
5. Normal sperm concentration of 15 million/mL and with normal motility of \> 40% according to World Health Organization cutoff points, in at least one ejaculate during the previous year

Exclusion Criteria:

1. Current pregnancy
2. Current use of hormonal contraception; use of any type of combined contraceptive or oral progestins within the past month; or use of hormonal implants or depo progestins within the past 3 months
3. Other known cause of infertility: endometriosis, tubal factor, uterine abnormalities
4. Uncorrected thyroid disease
5. Untreated hyperprolactinemia.
6. Medical conditions in which avoiding pregnancy is recommended until under improved control: poorly controlled Type 1 or Type 2 diabetes, poorly controlled hypertension
7. Contraindications to clomiphene citrate: hypersensitivity to CC or any of its components, history of liver disease or known liver disease, unknown cause of abnormal uterine bleeding, or intracranial lesion
8. Contraindications to letrozole: hypersensitivity to letrozole or any of its components.
9. Use of medications known to affect reproductive function or metabolism or that are an absolute contraindication during pregnancy within the past month.
10. If patients are suspected based on clinical findings for other etiologies that mimic PCOS, work up must be completed to exclude other etiologies prior to enrollment (i.e. Cushing's syndrome, androgen-secreting tumor).

Primary outcomes:
measure: Number of Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level
timeFrame: 7 days following LH surge or at cycle day 21 if no LH surge was detected
Secondary outcomes:
measure: Number of Developing Follicles
timeFrame: Cycle day 12-14
measure: Size of Largest Developing Follicle
timeFrame: Cycle day 12-14
measure: Endometrial Thickness
timeFrame: Cycle day 12-14
measure: Conception
timeFrame: 5 weeks after treatment
measure: Clinical Pregnancy
timeFrame: 6-7 weeks after treatment
measure: Multiple Gestation
timeFrame: 9-10 months after treatment
measure: Live Birth
timeFrame: 9-10 months after treatment
measure: Pregnancy Loss
timeFrame: 9-10 months after treatment
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
Study officials:
affiliation: University of Iowa Hosptials & Clinics
name: Rachel Mejia, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa Hospitals & Clinics
name: Brad Van Voorhis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mejia RB, Summers KM, Kresowik JD, Van Voorhis BJ. A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome. Fertil Steril. 2019 Mar;111(3):571-578.e1. doi: 10.1016/j.fertnstert.2018.11.030. Epub 2019 Jan 22.