Clinical trial NCT04325295: LOD vs Gn in Anovulatory PCOs Resistant to First Line Agents
Official title: Laparoscopic Ovarian Drilling Versus Gonadotrophins for Anovulatory Polycystic Ovary Syndrome Resistant to First Line Ovulation Induction: a Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Polycystic Ovary Syndrome
Anovulation
Keywords: Laparoscopic ovarian drilling
Gonadotrophins
Polycystic ovary syndrome
Anovulation
PCOs
Clomiphene resistant
Letrozole resistant
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-03-27
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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 .

Systematic reviews done comparing LOD to Gn found no differences in live birth, clinical pregnancy or miscarriage rates. However, there was significant decrease in OHSS and multiple pregnancies with LOD . Giving these advantages together with being cheap, the surgical strategy may be a more favorable choice as second line treatment of anovulation . Also several randomised controlled trial (RCTs) reported normalization of ovarian reserve parameters after LOD, making it a long-lasting option compared to the one-cycle effect of medical treatment 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

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Live Birth
timeFrame: within 12 months after of end treatment strategy
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Professor of obstetric and Gynecology,Faculty of Medicine,Assuit University O
name: Sayed A Abdallah
role: STUDY_DIRECTOR
affiliation: Assistant Professor of Obstetrics and Gynecology,Faculty of Medicine, Assuit University
name: Essam R Othman
role: STUDY_DIRECTOR
affiliation: Assistant professor of Obstetrics and Gynecology, Faculty of Medicine,Assuit University
name: Mustafa B Mohammed
role: STUDY_DIRECTOR
affiliation: Lecturer of Obstetrics and Gynecology,Faculty of Medicine,Assuit University
name: Ahmed M Alaa Eldin
role: STUDY_DIRECTOR
affiliation: Assistant lecturer of Obstetrics and Gynecology,Faculty of Medicine,Assuit University
name: Karim S Abdallah
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Api M. Is ovarian reserve diminished after laparoscopic ovarian drilling? Gynecol Endocrinol. 2009 Mar;25(3):159-65. doi: 10.1080/09513590802585605.
citation: 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.
citation: 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.
citation: 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.
citation: 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.