NCT06486870

Brief 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. 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
183

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jan 2020

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2020

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2024

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2024

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

June 27, 2024

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 5, 2024

Completed
Last Updated

July 5, 2024

Status Verified

June 1, 2024

Enrollment Period

4 years

First QC Date

June 27, 2024

Last Update Submit

June 27, 2024

Conditions

PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries

Keywords

gonadotropinletrozoleclomiphene citrateovarian drillingpregnancy rateovulation rate

Outcome Measures

Primary Outcomes (1)

  • pregnancy rate

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

    6 month

Secondary Outcomes (3)

  • ovulation rate

    6 months

  • multiple pregnancy rate

    6 months

  • miscarriage rate

    6 months

Study Arms (3)

gonadotropin

EXPERIMENTAL

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

letrozole

EXPERIMENTAL

: 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

unilateral laparoscopic ovarian drilling

EXPERIMENTAL

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

Interventions

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.

gonadotropin
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

letrozole
laparoscopic ovarian drillingPROCEDURE

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

unilateral laparoscopic ovarian drilling

Eligibility Criteria

Age20 Years - 35 Years
Sexfemale(Gender-based eligibility)
Gender Eligibility Detailsinfertile women from 20 to 35 years old with PCOS referred to gynecology and infertility clinics, Department of Obstetrics and Gynecology,Kasr Ainy Hospital , Cairo University. Infertile woman diagnosed to have PCO according to Rotterdam criteria as ovulatory disturbance, hyperandrogenism and presence of more than 12 follicles, 2- 9 mm in diameter in each other by ultrasound examination
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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)

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

faculty of medicine, Kasr el ainy hospital, Cairo university

Cairo, 11562, Egypt

Location

Related Publications (16)

  • 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.

    PMID: 31867117RESULT

  • 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.

    PMID: 22777527RESULT

  • 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.

    PMID: 27976369RESULT

  • 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.

    PMID: 34220713RESULT

  • 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.

    PMID: 26622481RESULT

  • 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.

    PMID: 25408702RESULT

  • 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.

    PMID: 25469124RESULT

  • 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.

    PMID: 18308833RESULT

  • 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.

    PMID: 17489756RESULT

  • 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.

    PMID: 23543241RESULT

  • 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.

    RESULT

  • 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.

    PMID: 21457973RESULT

  • 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.

    PMID: 16543255RESULT

  • 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.

    RESULT

  • 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.

    PMID: 22768457RESULT

  • Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B. Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. J Assist Reprod Genet. 2009 Jan;26(1):19-24. doi: 10.1007/s10815-008-9284-4. Epub 2009 Jan 7.

    PMID: 19127427RESULT

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

GonadotropinsLetrozole

Condition Hierarchy (Ancestors)

Ovarian CystsCystsNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGonadal DisordersEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNitrilesOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Mamdouh Sheeba, MD

    kasr alainy, Cairo university

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
lecturer

Study Record Dates

First Submitted

June 27, 2024

First Posted

July 5, 2024

Study Start

January 1, 2020

Primary Completion

January 1, 2024

Study Completion

January 31, 2024

Last Updated

July 5, 2024

Record last verified: 2024-06

Data Sharing

IPD Sharing
Will not share

Locations

EG(1)