Comparison Between Two Ovulation Induction Therapies and LOD on Clinical Outcomes in CC-Resistant PCOS Women

June 27, 2024 updated by: ahmed nagy shaker ramadan, Cairo University

Comparative Study Between Two Ovulation Induction Therapies and Laparoscopic Ovarian Drilling on Clinical Outcomes in Clomiphene Citrate-Resistant PCOS Women

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting 4-8% of reproductive-aged women and is a leading cause of infertility due to oligo-anovulation (1). Studies suggest a higher prevalence of 17.8-19.9% based on Rotterdam diagnostic criteria. PCOS is diagnosed by the presence of at least two out of three criteria: oligo- and/or anovulation, hyperandrogenism, and polycystic ovaries, with other etiologies excluded (2). Clomiphene citrate (CC), a selective estrogen receptor modulator, has been the first-line treatment for inducing ovulation in anovulatory women with PCOS for decades. Approximately 80% of women resume ovulation with CC, but only 35-40% achieve pregnancy. About 15-40% of women are resistant to CC, defined as failure to ovulate after receiving a maximum dosage of 150 mg per day for 5 days starting on the third day of the menstrual cycle. For CC-resistant women, metformin, an insulin sensitizer, has been explored but shows limited effectiveness except in combination with CC. Gonadotropins are the standard treatment for CC-resistant PCOS but come with risks of multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) (3). Letrozole, an aromatase inhibitor, is another treatment option that prevents the conversion of androgens to estrogen, thereby increasing gonadotropin-releasing hormone (GnRH) secretion and promoting ovulation. Letrozole has shown superior ovulation and live birth rates compared to CC and is now recommended as the first-line treatment for anovulation in women with PCOS. It has comparable rates of OHSS and miscarriage to CC, but fewer relevant studies have compared it directly to laparoscopic ovarian drilling (LOD) (4). LOD is an alternative to gonadotropins for inducing ovulation in CC-resistant PCOS. It involves surgical intervention, which can be either unilateral or bilateral, and is effective without the risks of multiple pregnancies or OHSS. LOD also increases ovarian responsiveness to CC. Despite minimal morbidity, LOD can lead to tubo-ovarian adhesions and premature ovarian failure, although these risks are reduced by careful technique (5).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

### Materials and Methods

**Design:** A randomized clinical study to evaluate and compare the effects of gonadotropins, Letrozole, and unilateral laparoscopic ovarian drilling in infertile women with PCOS. Conducted at Kasr El Aini Maternity Hospital, Cairo University, gynecological and infertility clinics.

**Patients:** The study includes infertile women aged 20-35 years with PCOS referred to the gynecology and infertility clinics of the Department of Obstetrics and Gynecology, Kasr Ainy Hospital, Cairo University. Women diagnosed with PCOS based on the Rotterdam criteria (ovulatory disturbance, hyperandrogenism, and the presence of more than 12 follicles, 2-9 mm in diameter, in each ovary by ultrasound examination) are randomly assigned to one of three groups: Letrozole (G1), Gonadotropin (G2), or Laparoscopic Unilateral Ovarian Drilling (G3), based on a computer-generated random number sequence. Side effects for each intervention are registered.

**Treatment Protocol:**

  • Group I (G1): Letrozole 2.5 mg oral tablets, administered from the fifth day of menses for 5 days, repeated for up to six cycles.
  • Group II (G2): Human menopausal gonadotropin (hMG) starts on cycle day three, 75 IU every other day, aiming for mono-ovulation. Monitoring through transvaginal ultrasound begins on cycle day nine. The hMG dose is adjusted based on follicular response. Cycles are cancelled for under or over-response.
  • Group III (G3): Laparoscopic ovarian drilling with electrocautery (mixed current, monopolar electrosurgical needle, 4-point cauterization, each for 4 seconds, 40 W, 3 mm diameter, 4 mm depth) on one ovary.

**Follow-Up:** Patients will be monitored for six months post-intervention. Hormonal profiles will be reassessed at the end of the study period. Statistical analyses will be performed using Microsoft Excel 2007 and IBM SPSS version 22. A p-value <0.05 will be considered statistically significant.

Study Type

Interventional

Enrollment (Actual)

183

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt, 11562
        • faculty of medicine, Kasr el ainy hospital, Cairo university

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 20 to 35 years
  • Infertile woman diagnosed to have PCO according to Rotterdam criteria as ovulatory distrbance, hyperandrogenism and presence of more than 12 follicles, 2- 9 mm in diameter in each other by ultrasound examination
  • Resistance to clomiphene citrate i.e failed to respond to clomiphene citrate dose up to 150 mg per day for at least 3 cycles
  • BMI from18-30
  • High LH/FSH ratio≥1.5 , LH level ≥10IU/l)

Exclusion Criteria:

  • Extremes of age less than 20 years old or more than 35 years old
  • Hormonal therapy and oral contraception for the past 3cycle
  • Other causes of infertility including tubal , uterine and male causes .
  • Pre-existing endocrine disease including thyroid disorder, cushing's syndrome and congenital adrenal hyperplasia
  • Any previous version surgery
  • Obese patients with BMI >35
  • Low ovarian reserve by AMH serum level measurement (AMH < .5-1.1 ng/ml).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: gonadotropin
Human menopausal gonadotrophin (hMG) is given starting on cycle day three in a dose of 75 IU alternate days. The aim of treatment is to achieve mono-ovulation. Monitoring of treatment is achieved by serial transvaginal ultrasound scanning every other day starting from cycle day nine. Size and number of follicles is recorded in patients follow up sheets. The dose of hMG is reviewed around stimulation day 10 and if follicular development is unsatisfactory, the dose is increased to 75 IU daily .If a good response is not achieved day16 ; the cycle is cancelled. A new cycle is commenced with a higher starting dose of hMG (75 IU per day). When one follicle reached a size of > =18 mm a single dose of 10,000 IU human chorionic gonadotrophin (hCG, Pregnyl, Epifasi, Choriomon) is given.
Drug: Gonadotropin
Human menopausal gonadotrophin (hMG) is given starting on cycle day three in a dose of 75 IU alternate days. The aim of treatment is to achieve mono-ovulation. Monitoring of treatment is achieved by serial transvaginal ultrasound scanning every other day starting from cycle day nine. Size and number of follicles is recorded in patients follow up sheets. The dose of hMG is reviewed around stimulation day 10 and if follicular development is unsatisfactory, the dose is increased to 75 IU daily .If a good response is not achieved day16 ; the cycle is cancelled. A new cycle is commenced with a higher starting dose of hMG (75 IU per day). When one follicle reached a size of > =18 mm a single dose of 10,000 IU human chorionic gonadotrophin (hCG, Pregnyl, Epifasi, Choriomon) is given.
Experimental: letrozole
: 5 mg LE oral tablets are administered on the fifth day of menses and then every day for 5 days. Treatment is repeated for up to six cycles
Drug: Letrozole
5 mg LE oral tablets are administered on the fifth day of menses and then every day for 5 days. Treatment is repeated for up to six cycles
Experimental: unilateral laparoscopic ovarian drilling

Laparoscopic ovarian drilling will be done according to the following:

Electrocautery using a mixed current in monopolar electrosurgical needle will be into introduced through the ovarian ipsilateral parts and applied up to 4 point cauterisation of the ovarian capsule, each for 4 second, at 40 W and for a diameter of 3mm and a depth of 4 mm in the antimesentric surface . (Amer et al 2003, Sawant S et al 2019) ,the procedure will be applied for one ovary .

The patient under the study will be followed up to six months of continuous marital life after the procedure
Procedure: laparoscopic ovarian drilling

Laparoscopic ovarian drilling will be done according to the following:

Electrocautery using a mixed current in monopolar electrosurgical needle will be into introduced through the ovarian ipsilateral parts and applied up to 4 point cauterisation of the ovarian capsule, each for 4 second, at 40 W and for a diameter of 3mm and a depth of 4 mm in the antimesentric surface . (Amer et al 2003, Sawant S et al 2019) ,the procedure will be applied for one ovary .

The patient under the study will be followed up to six months of continuous marital life after the procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pregnancy rate
Time Frame: 6 month
identified by serum β-HCG of >50 IU/L and gestational sac seen on ultrasound.
6 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ovulation rate
Time Frame: 6 months
The ovulation rate refers to the percentage of women who successfully ovulate after a particular treatment regimen during a specified time period.
6 months
multiple pregnancy rate
Time Frame: 6 months
The multiple pregnancy rate refers to the percentage of pregnancies that result in the birth of more than one baby, such as twins, triplets, or higher-order multiples, following a particular fertility treatment.
6 months
miscarriage rate
Time Frame: 6 months
The miscarriage rate refers to the percentage of pregnancies that end in miscarriage, defined as the spontaneous loss of a pregnancy before the fetus reaches viability (usually before 20 weeks of gestation).
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cairo University

Investigators

  • Study Director: Mamdouh Sheeba, MD, Kasr Alainy, Cairo University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2020

Primary Completion (Actual)

January 1, 2024

Study Completion (Actual)

January 31, 2024

Study Registration Dates

First Submitted

June 27, 2024

First Submitted That Met QC Criteria

June 27, 2024

First Posted (Actual)

July 5, 2024

Study Record Updates

Last Update Posted (Actual)

July 5, 2024

Last Update Submitted That Met QC Criteria

June 27, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AA-2024-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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