IVF Outcome Following Progestogen Ovarian Stimulation

IVF Clinical Trial

Official title:

Role Of Dydrogesterone Towards Oocyte and Embryo Quality in Polycystic Ovarian Syndrome (PCOS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04175990
• Other study ID #: UKMPPI/111/8/JEP-2018-165
• Status: Completed
• Phase: Phase 1
• Start date: May 10, 2018
• Est. completion date: May 9, 2019

Study information

• Verified date: November 2019
• Source: National University of Malaysia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a prospective controlled cohort study conducted at the Department of Medical Assisted Conception (MAC) unit of the University Kebangsaan Malaysia Medical Centre (UKMMC). From May 2018 through May 2019, women with Polycystic Ovarian Syndrome (PCOS) undergoing IVF/intracytoplasmic sperm insemination(ICSI) regimens for the treatment of infertility were recruited.

Patients recruited will then be randomized accordingly using the randomizer software. Group A will be the interventional group and group B will be the control group.

Oocyte retrieval will be performed 34-36 hours following the human chorionic gonadotrophin (hCG) trigger. Sperm was obtained on the same day. Mature oocytes will be fertilized with sperm via IVF or ICSI. Fertilized embryos were observed via time laps method and the progress and cleavage were monitored before planning for embryo transfer. Embryo transfer will be performed on day 3 or day 5 after oocyte retrieval.

All results will be analyzed using Statistical Package for the Social Sciences(SPSS) version 21 software. Descriptive analysis will be done for demographic data and presented in mean ± Standard deviation (SD). Demographic characteristic between the two groups will be compared with the use of the Mann-Whitney U test. The categorical data was analysed by using Chi-square test for the association of variables. A p-value of 0.05 or less was considered to be significant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: May 9, 2019
• Est. primary completion date: March 10, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• · 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dydrogesterone Pill
started from day 1 of menses till trigger day

Locations

Country	Name	City	State
Malaysia	Medically Assisted Conception Unit, Ukm Medical Centre	Cheras	Kuala Lumpur

Sponsors (1)

Lead Sponsor	Collaborator
National University of Malaysia

Country where clinical trial is conducted

Malaysia, 

References & Publications (15)

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

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:CD001750. doi: 10.1002/14651858.CD001750.pub4. Review. — View Citation

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. Review. — View Citation

Bosch E, Valencia I, Escudero E, Crespo J, Simón C, Remohí 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. — View Citation

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 Institu — View Citation

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 fertilizati — View 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. Review. — View Citation

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

Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab. 2003 Oct;14(8):365-70. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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). — View Citation

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 Repr — View Citation

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. — View Citation

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: 10.1 — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of oocyte retrieval	number of oocyte retrieved	30 hour after trigger with HCG 10000 International unit (IU)
Primary	Biochemical pregnancy rate	serum Bhcg more than 5 mol/L	14 days after embryo transferred
Primary	clinical pregnancy rate	presence of intrauterine gestational sac	4 weeks after embryo transfer