Clinical trial · Interventional
Comparison Between Two Ovulation Induction Therapies and LOD on Clinical Outcomes in CC-Resistant PCOS Women
Comparative Study Between Two Ovulation Induction Therapies and Laparoscopic Ovarian Drilling on Clinical Outcomes in Clomiphene Citrate-Resistant PCOS Women
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries | — | UNRESOLVED | — |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Gonadotropin | Drug | — | UNRESOLVED |
| laparoscopic ovarian drilling | Procedure | — | UNRESOLVED |
| Letrozole | Drug | Letrozole | ALIAS |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- gonadotropin
- description
- 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.
- interventionNames
- Drug: Gonadotropin
- type
- EXPERIMENTAL
- label
- letrozole
- description
- : 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
- interventionNames
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 20 Years
- Maximum age
- 35 Years
Show eligibility criteria text
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).
References
Publications (16)
- RESULTThomas 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. PMID 31867117
- RESULTYildiz 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. PMID 22777527
- RESULTBrown 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. PMID 27976369
- RESULTYang 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. PMID 34220713
- RESULTLiu 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. PMID 26622481
- RESULTMoazami 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. PMID 25408702
- RESULTDavar 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.