LOD vs Gn in Anovulatory PCOs Resistant to First Line Agents

NCT04325295 | Unknown

• 1 other identifier: induction resistant PCOs
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

PCOS is a complex disease that is diagnosed by the presence of two of the following three: oligo/anovulation, clinical and/or biochemical hyperandrogenism, or polycystic ovaries by ultrasound . PCOS affects 4% to 21% of females in reproductive age . Although subfertility is abundant in women with PCOS, a majority of these women will achieve pregnancy naturally or by treatment. Different treatment modalities are present for ovulation induction. Life style modifications including weight loss are encouraged for those who are overweight or obese. Pharmacological induction of ovulation represent the first line therapy for induction of ovulation. Options include aromatase inhibitors (Letrozole), Clomiphene Citrate (CC) or Metformin, alone or in combinations. For second line treatment either Gonadotropins (Gn) or laparoscopic ovarian surgery (LOS) are the recommended options . the objective of the trial is to study the effectiveness and safetey of surgical induction of ovulation strategy and compare it to medical induction strategy with Gonadotropins

Conditions

Polycystic Ovary Syndrome; Anovulation

Keywords

Laparoscopic ovarian drilling; Gonadotrophins; Polycystic ovary syndrome; Anovulation; PCOs; Clomiphene resistant; Letrozole resistant

Outcome Measures

Primary Outcomes (1)

• Live Birth

  defined as the number of births resulted in live babies after the age of viability (24th week of pregnancy)

  within 12 months after of end treatment strategy

Study Arms (2)

Surgical treatment strategy:

ACTIVE COMPARATOR

Procedure: Laparoscopic ovarian drilling

Gonadotrophins treatment strategy

ACTIVE COMPARATOR

Drug: Recombinant FSH (rFSH)

Interventions

Laparoscopic ovarian drilling PROCEDURE

LOD will be done in the follicular phase.Follow up will be done on the next cycle by performing a TVUS examination at CD 13 and measuring the dominant follicles. Ovulation is considered if a follicle reached \> 17 mm and is confirmed by measuring serum progesterone at CD 21.If ovulation is not achieved in the cycle following LOD, women will be prescribed Letrozole by the dose of 2.5 mg daily for 5 days starting from CD 3, and ovulation monitoring will be done similarly. If ovulation is not achieved, the dose is increased by 2.5 mg daily in the subsequent cycle until reaching the maximum dose of 7.5 mg daily for a total of 3 cycles.With persistent resistance to Letrozole in inducing ovulation, Gn will be prescribed for 3 cycles as in Gonadotrophin strategy

Surgical treatment strategy:

Recombinant FSH (rFSH) DRUG

A low-dose step-up protocol will be implemented. This starts on CD 3,The rFSH will be given through (IM) or(SC) injections with 75 IU and will be given once daily.Monitoring of the treatment will be done on CD 7 by TVUS and serum E2. Monitoring is individualized according to the response. Depending on the response and follicular growth, the dose may be adjusted by increasing 37.5 IU. If follicular growth failed, the dose is furtherly increased by the same amount until at least one follicle reaches 10 mm. The dose is maintained until at least one follicle reaches a diameter of 18 mm and no more than 2 follicles are bigger than 15 mm. Once reaching the desired diameter, the rFSH will be stopped and a trigger of ovulation by an IM injection of 5000 IU of hCG and sexual intercourse is encouraged on the day of trigger and the next day. Then serum P will be done 7 days after hCG injection to detect the occurrence of ovulation.

Gonadotrophins treatment strategy

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• anovulatory polycystic ovary syndrome resistant to first line ovulation induction.
• Polycystic ovary Syndrome defined by Rotterdam's criteria 2003
• Clomiphene resistance defined as failure to ovulate with a dose of 150mg per day for 5 days for 3 cycles
• Letrozole resistance defined as failure to ovulate with a dose of 7.5 mg per day for 5 days for 3 cycles

You may not qualify if:

• women's age \< 18 years or ≥ 40 years.
• BMI \> 40 kg/m2
• Patient with hyperprolactinaemia (serum prolactin above normal limits)
• Patients with hypogonadotropic hypogonadism (low serum FSH and LH)
• Patients with anovulation due to ovarian failure (serum FSH higher than normal limits)
• Male infertility
• Tubal abnormality, Known endometriosis, adenomyosis, uterine myomas or any other detected cause of female infertility
• History of ovarian surgery as laparoscopic ovarian drilling, ovarian cystectomy or oophorectomy
• History of pelvic radiation
• Patient recently treated with any type of induction of ovulation in the last three months.

Sponsors & Collaborators

• Assiut University: lead

Related Publications (9)

• Farquhar CM, Bhattacharya S, Repping S, Mastenbroek S, Kamath MS, Marjoribanks J, Boivin J. Female subfertility. Nat Rev Dis Primers. 2019 Jan 24;5(1):7. doi: 10.1038/s41572-018-0058-8.

  PMID: 30679436 BACKGROUND

• Weiss NS, Kostova E, Nahuis M, Mol BWJ, van der Veen F, van Wely M. Gonadotrophins for ovulation induction in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2019 Jan 16;1(1):CD010290. doi: 10.1002/14651858.CD010290.pub3.

  PMID: 30648738 BACKGROUND

• Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016 Jul;106(1):6-15. doi: 10.1016/j.fertnstert.2016.05.003. Epub 2016 May 24.

  PMID: 27233760 BACKGROUND

• van Wely M, Bayram N, Bossuyt PM, van der Veen F. Laparoscopic electrocautery of the ovaries versus recombinant FSH in clomiphene citrate-resistant polycystic ovary syndrome. Impact on women's health-related quality of life. Hum Reprod. 2004 Oct;19(10):2244-50. doi: 10.1093/humrep/deh406. Epub 2004 Jul 8.

  PMID: 15242999 BACKGROUND

• Api M. Is ovarian reserve diminished after laparoscopic ovarian drilling? Gynecol Endocrinol. 2009 Mar;25(3):159-65. doi: 10.1080/09513590802585605.

  PMID: 19347705 BACKGROUND

• Debras E, Fernandez H, Neveu ME, Deffieux X, Capmas P. Ovarian drilling in polycystic ovary syndrome: Long term pregnancy rate. Eur J Obstet Gynecol Reprod Biol X. 2019 Aug 13;4:100093. doi: 10.1016/j.eurox.2019.100093. eCollection 2019 Oct.

  PMID: 31497757 BACKGROUND

• Amer SA, Banu Z, Li TC, Cooke ID. Long-term follow-up of patients with polycystic ovary syndrome after laparoscopic ovarian drilling: endocrine and ultrasonographic outcomes. Hum Reprod. 2002 Nov;17(11):2851-7. doi: 10.1093/humrep/17.11.2851.

  PMID: 12407038 BACKGROUND

• Farquhar C, Brown J, Marjoribanks J. Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2012 Jun 13;(6):CD001122. doi: 10.1002/14651858.CD001122.pub4.

  PMID: 22696324 BACKGROUND

• Nahuis MJ, Oude Lohuis E, Kose N, Bayram N, Hompes P, Oosterhuis GJ, Kaaijk EM, Cohlen BJ, Bossuyt PP, van der Veen F, Mol BW, van Wely M. Long-term follow-up of laparoscopic electrocautery of the ovaries versus ovulation induction with recombinant FSH in clomiphene citrate-resistant women with polycystic ovary syndrome: an economic evaluation. Hum Reprod. 2012 Dec;27(12):3577-82. doi: 10.1093/humrep/des336. Epub 2012 Sep 20.

  PMID: 23001778 BACKGROUND

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Anovulation

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Sayed A Abdallah

  Professor of obstetric and Gynecology,Faculty of Medicine,Assuit University O

  STUDY DIRECTOR

• Essam R Othman

  Assistant Professor of Obstetrics and Gynecology,Faculty of Medicine, Assuit University

  STUDY DIRECTOR

• Mustafa B Mohammed

  Assistant professor of Obstetrics and Gynecology, Faculty of Medicine,Assuit University

  STUDY DIRECTOR

• Ahmed M Alaa Eldin

  Lecturer of Obstetrics and Gynecology,Faculty of Medicine,Assuit University

  STUDY DIRECTOR

• Karim S Abdallah

  Assistant lecturer of Obstetrics and Gynecology,Faculty of Medicine,Assuit University

  STUDY DIRECTOR

Central Study Contacts

Khaled M Attyia

CONTACT

+201005503250; khaled.hussien@med.aun.edu.eg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 26, 2020
• First Posted: March 27, 2020
• Study Start: December 1, 2020
• Primary Completion: June 1, 2022
• Study Completion: August 1, 2022
• Last Updated: October 14, 2020

Record last verified: 2020-10