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PCOS (Polycystic Ovary Syndrome) of Bilateral OvariesPhase 3NCT06486870

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

A Phase 3 study testing Gonadotropin, Letrozole and laparoscopic ovarian drilling in people with PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, run by Cairo University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 20 to 35 years, women only
What is being tested?
Gonadotropin, Letrozole and laparoscopic ovarian drilling
Could I receive a placebo?
No, everyone receives an active treatment
How many people
183 participants
Where
1 siteEgypt
Study dates
1 Jan 2020to 31 Jan 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 35 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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)

Who cannot join

  • 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).

Trial locations and contacts

1 site in 1 country.

Egypt1 site

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

    Cairo, 11562

Other trials in Egypt

About this study

Official title: 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).

Read the 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.

Being tested
Gonadotropin, Letrozole, laparoscopic ovarian drilling
Keywords
gonadotropin, letrozole, clomiphene citrate, ovarian drilling, pregnancy rate, ovulation rate
Medical subject headings
Polycystic Ovary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GonadotropinDrug

    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.

  • LetrozoleDrug

    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

  • laparoscopic ovarian drillingProcedure or surgery

    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

Study groups in NCT06486870
Study groupRoleWhat they receive
gonadotropinExperimentalHuman 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.
Receives: Drug: Gonadotropin
letrozoleExperimental: 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
Receives: Drug: Letrozole
unilateral laparoscopic ovarian drillingExperimentalLaparoscopic 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
Receives: Procedure: laparoscopic ovarian drilling

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. pregnancy rate

    identified by serum β-HCG of >50 IU/L and gestational sac seen on ultrasound.

    Measured: 6 month

Secondary outcomes (3)

  1. ovulation rate

    The ovulation rate refers to the percentage of women who successfully ovulate after a particular treatment regimen during a specified time period.

    Measured: 6 months

  2. multiple pregnancy rate

    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.

    Measured: 6 months

  3. miscarriage rate

    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).

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2024
  2. Study start1 Jan 2020
  3. Primary completion1 Jan 2024
  4. Study completion31 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
183 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06486870
Sponsor's protocol ID
AA-2024-2
Status last verified
Jun 2024
First submitted
27 Jun 2024
Last updated
5 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Thomas S, Woo I, Ho J, Jones T, Paulson R, Chung K, Bendikson K. Ovulation rates in a stair-step protocol with Letrozole vs clomiphene citrate in patients with polycystic ovarian syndrome. Contracept Reprod Med. 2019 Dec 9;4:20. doi: 10.1186/s40834-019-0102-4. eCollection 2019.

    PubMed 31867117

  • Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012 Oct;27(10):3067-73. doi: 10.1093/humrep/des232. Epub 2012 Jul 9.

    PubMed 22777527

  • Brown J, Farquhar C. Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome. Cochrane Database Syst Rev. 2016 Dec 15;12(12):CD002249. doi: 10.1002/14651858.CD002249.pub5.

    PubMed 27976369

  • Yang AM, Cui N, Sun YF, Hao GM. Letrozole for Female Infertility. Front Endocrinol (Lausanne). 2021 Jun 16;12:676133. doi: 10.3389/fendo.2021.676133. eCollection 2021.

    PubMed 34220713

  • Liu W, Dong S, Li Y, Shi L, Zhou W, Liu Y, Liu J, Ji Y. Randomized controlled trial comparing letrozole with laparoscopic ovarian drilling in women with clomiphene citrate-resistant polycystic ovary syndrome. Exp Ther Med. 2015 Oct;10(4):1297-1302. doi: 10.3892/etm.2015.2690. Epub 2015 Aug 19.

    PubMed 26622481

  • Moazami Goudarzi Z, Fallahzadeh H, Aflatoonian A, Mirzaei M. Laparoscopic ovarian electrocautery versus gonadotropin therapy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome: A systematic review and meta-analysis. Iran J Reprod Med. 2014 Aug;12(8):531-8.

    PubMed 25408702

  • Davar R, Tabibnejad N, Kalantar SM, Sheikhha MH. The luteinizing hormone beta-subunit exon 3 (Gly102Ser) gene mutation and ovarian responses to controlled ovarian hyperstimulation. Iran J Reprod Med. 2014 Oct;12(10):667-72.

    PubMed 25469124

  • Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008 Mar;23(3):462-77. doi: 10.1093/humrep/dem426.

    PubMed 18308833

  • Godinjak Z, Javoric R. Clinical outcome and hormone profiles before and after laparoscopic electroincision of the ovaries in women with polycystic ovary syndrome. Bosn J Basic Med Sci. 2007 May;7(2):171-5. doi: 10.17305/bjbms.2007.3076.

    PubMed 17489756

  • Abu Hashim H, Al-Inany H, De Vos M, Tournaye H. Three decades after Gjonnaess's laparoscopic ovarian drilling for treatment of PCOS; what do we know? An evidence-based approach. Arch Gynecol Obstet. 2013 Aug;288(2):409-22. doi: 10.1007/s00404-013-2808-x. Epub 2013 Mar 30.

    PubMed 23543241

  • Ibrahim MH, Tawfic M, Hassan MM, Sedky OH. Letrozole versus laparoscopic ovarian drilling in infertile women with PCOS resistant to clomiphene citrate. Middle East Fertility Society Journal. 2017 Dec 1;22(4):251-4.

  • Abdellah MS. Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome. Int J Gynaecol Obstet. 2011 Jun;113(3):218-21. doi: 10.1016/j.ijgo.2010.11.026. Epub 2011 Apr 1.

    PubMed 21457973

  • Elnashar A, Abdelmageed E, Fayed M, Sharaf M. Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study. Hum Reprod. 2006 Jul;21(7):1805-8. doi: 10.1093/humrep/del053. Epub 2006 Mar 16.

    PubMed 16543255

  • Yadav P, Singh S, Singh R, Jain M, Awasthi S, Raj P. To study the effect on fertility outcome by gonadotropins vs laparoscopic ovarian drilling in clomiphene-resistant cases of polycystic ovarian syndrome. Journal of the South Asian Federation of Obstetrics and Gynaecology. 2017 Oct;9(4):336-40.

  • Mehrabian F, Eessaei F. The laparoscopic ovarian electrocautery versus gonadotropin therapy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome; a randomized controlled trial. J Pak Med Assoc. 2012 Mar;62(3 Suppl 2):S42-4.

    PubMed 22768457

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Gonadotropin, Letrozole and laparoscopic ovarian drilling in people with PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, run by Cairo University at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

pregnancy rate (time frame: 6 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06486870, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2024.

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