IVF Outcome Following Progestogen Ovarian Stimulation

NCT04175990 | Completed Phase 1

• 1 other identifier: UKMPPI/111/8/JEP-2018-165
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

Brief Summary

The new strategy is by using the progestogen to block the luteinizing hormone(LH) surge either endogenous during luteal phase stimulation, or exogenous in the follicular phase i.e progestin primed ovarian stimulation (PPOS). The goal of PPOS is to develop a single dominant follicle. Various types of oral Progestin had been studied before including Medroxyprogesterone Acetate (MPA) and Utrogestan with different dosage. A different study by Wang et al conducted by using MPA to patients with PCOS. The use of MPA is contraindicated in human pregnancy whereas Dydrogesterone had been extensively used worldwide for the treatment of threatened miscarriage as well as luteal support in infertility setting. Previous protocol on PPOS showed inconclusive results. Therefore in this study, Dydrogesterone was used as the Progestin Primed Ovarian hyperstimulation to explore its effect on PCOS women IVF outcome.

Conditions

IVF; Oocyte Maturation Defect 1; Clinical Pregnancy Rate; Ovarian Hyperstimulation

Keywords

progestogen; ovarian stimulation regime; IVF outcome

Outcome Measures

Primary Outcomes (3)

• Number of oocyte retrieval

  number of oocyte retrieved

  30 hour after trigger with HCG 10000 International unit (IU)

• Biochemical pregnancy rate

  serum Bhcg more than 5 mol/L

  14 days after embryo transferred

• clinical pregnancy rate

  presence of intrauterine gestational sac

  4 weeks after embryo transfer

Study Arms (2)

Progestogen

EXPERIMENTAL

Oral Dydrogesterone 10mg tds was given from day 1 of menses till day of trigger

Drug: Dydrogesterone Pill

standard combine minimal stimulation protocol

NO INTERVENTION

Oral clomiphene citrate 100mg daily given from day 1 till day 10 of menses with additional gonadotrophin (Menopur 225mg daily) from day 3 of menses till trigger day

Interventions

Dydrogesterone Pill DRUG

started from day 1 of menses till trigger day

Progestogen

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• · Aged 20 - 40 years old
• Basal serum follicular stimulating hormone(FSH) level of no more than 10 IU/L
• Diagnosis of PCOS met using Rotterdam criteria.

You may not qualify if:

• low AMH level (AMH less than 3 ng/ml).
• Contraindicated to ovarian stimulation treatment eg: history of severe ovarian hyper stimulation syndrome(OHSS)
• Presence of uterine pathology eg: adenomyosis, large uterine fibroid.
• Patients who has had poor ovarian stimulation of twice or more.

Sponsors & Collaborators

• National University of Malaysia: lead

Study Sites (1)

Medically Assisted Conception Unit, Ukm Medical Centre

Cheras, Kuala Lumpur, 56000, Malaysia

Location

Related Publications (15)

• 7. Neill JD. Knobil and Neill's physiology of reproduction. 3rd edition. San Diego, CA: Elsevier, 2006: 1289-301

  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 RESULT

• Boomsma CM, Fauser BC, Macklon NS. Pregnancy complications in women with polycystic ovary syndrome. Semin Reprod Med. 2008 Jan;26(1):72-84. doi: 10.1055/s-2007-992927.

  PMID: 18181085 RESULT

• Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab. 2003 Oct;14(8):365-70. doi: 10.1016/j.tem.2003.08.002.

  PMID: 14516934 RESULT

• Shah DK, Missmer SA, Berry KF, Racowsky C, Ginsburg ES. Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization. Obstet Gynecol. 2011 Jul;118(1):63-70. doi: 10.1097/AOG.0b013e31821fd360.

  PMID: 21691164 RESULT

• Zhu X, Ye H, Fu Y. The Utrogestan and hMG protocol in patients with polycystic ovarian syndrome undergoing controlled ovarian hyperstimulation during IVF/ICSI treatments. Medicine (Baltimore). 2016 Jul;95(28):e4193. doi: 10.1097/MD.0000000000004193.

  PMID: 27428219 RESULT

• Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016 Apr 29;4(4):CD001750. doi: 10.1002/14651858.CD001750.pub4.

  PMID: 27126581 RESULT

• van der Spuy ZM, Dyer SJ. The pathogenesis of infertility and early pregnancy loss in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004 Oct;18(5):755-71. doi: 10.1016/j.bpobgyn.2004.06.001.

  PMID: 15380145 RESULT

• Bosch E, Valencia I, Escudero E, Crespo J, Simon C, Remohi J, Pellicer A. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome. Fertil Steril. 2003 Dec;80(6):1444-9. doi: 10.1016/j.fertnstert.2003.07.002.

  PMID: 14667881 RESULT

• Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.

  PMID: 25956370 RESULT

• Wang Y, Chen Q, Wang N, Chen H, Lyu Q, Kuang Y. Controlled Ovarian Stimulation Using Medroxyprogesterone Acetate and hMG in Patients With Polycystic Ovary Syndrome Treated for IVF: A Double-Blind Randomized Crossover Clinical Trial. Medicine (Baltimore). 2016 Mar;95(9):e2939. doi: 10.1097/MD.0000000000002939.

  PMID: 26945402 RESULT

• Zhu X, Zhang X, Fu Y. Utrogestan as an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Medicine (Baltimore). 2015 May;94(21):e909. doi: 10.1097/MD.0000000000000909.

  PMID: 26020402 RESULT

• McCartney CR, Marshall JC. CLINICAL PRACTICE. Polycystic Ovary Syndrome. N Engl J Med. 2016 Jul 7;375(1):54-64. doi: 10.1056/NEJMcp1514916.

  PMID: 27406348 RESULT

• Diamond MP, Kruger M, Santoro N, Zhang H, Casson P, Schlaff W, Coutifaris C, Brzyski R, Christman G, Carr BR, McGovern PG, Cataldo NA, Steinkampf MP, Gosman GG, Nestler JE, Carson S, Myers EE, Eisenberg E, Legro RS; Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network. Endometrial shedding effect on conception and live birth in women with polycystic ovary syndrome. Obstet Gynecol. 2012 May;119(5):902-8. doi: 10.1097/AOG.0b013e31824da35c.

  PMID: 22525900 RESULT

• Wei D, Shi Y, Li J, Wang Z, Zhang L, Sun Y, Zhou H, Xu Y, Wu C, Liu L, Wu Q, Zhuang L, Du Y, Li W, Zhang H, Legro RS, Chen ZJ. Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome. Hum Reprod. 2017 Feb;32(2):354-361. doi: 10.1093/humrep/dew325. Epub 2016 Dec 19.

  PMID: 27999118 RESULT

MeSH Terms

Interventions

Dydrogesterone

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Muhammad azrai abu, medical Degree

  Department of Obstetrics and Gynecology, UKM Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: November 25, 2019
• Study Start: May 10, 2018
• Primary Completion: March 10, 2019
• Study Completion: May 9, 2019
• Last Updated: November 26, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)