Luteal Phase Support In IVF Women Using GnRH Agonist

IVF Clinical Trial

Official title:

A Comparison Of Progestogens Plus GnRH Agonist Versus Progestogens Only In Luteal Phase Support In IVF Women: A Retrospective Single Centre Experience

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04174378
• Other study ID #: PPI/111/8/JEP-2018-619
• Status: Completed
• Start date: November 29, 2018
• Est. completion date: November 18, 2019

Study information

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

Clinical Trial Summary

Lately, the role of GnRH agonist as luteal phase support has been recommended by various studies though the mechanism is still debatable. It has been postulated that GnRH agonist might support the corpus luteum by stimulating the secretion of luteinizing hormone by pituitary gonadotroph cells, or by acting directly on the endometrium through the locally expressed receptors.

Therefore, this study was designed to evaluate effects of the additional of single-dose GnRH agonist to the routine progestogens use for luteal phase support on IVF outcome as compared to progestogens only. The biochemical pregnancy rates, clinical pregnancy rates, live birth rates and miscarriage rate between these regimes were compared. The hypothesis of this study was women with addition of GnRH agonist as luteal phase support have higher biochemical pregnancy rate, clinical pregnancy rate and live birth rate compare to patient with progestogens only luteal phase support.

Description:

This was a retrospective study on selected patients who underwent IVF treatment under MAC (Medically Assisted Conception) Unit, University Kebangsaan Malaysia Medical Centre for the period of June 2015-June 2018. Their medical records were reviewed, and data analysed.

The sample size was calculated using Power & Sample Size Calculator by Dupont & Plummer 1998 for dichotomous response version 3.1.2 [6]. Based on this formula, a is the type I error probability for a two-sided test allowable about 5% in this study. The power of certainty is the percentage of estimated power of this study. On the other hand, p0 is the probability of the outcome for GnRH agonist used as luteal phase support by Zafardoust et al. [7] which is 30% (0.30). The p1 is the probability of the outcome in an experimental subject which expected in this study based on similar objective of higher rate of implantation with GnRH agonist. The investigators set the p1 is 0.50 as overall literature suggest that at cumulative successful of implantation post GnRH is around 30-50%. The m is the ratio of control to experimental subjects which is 1 to 1 in this study. Generated sample size from this program is 93 for one arm which result in total sample size is 186. The investigators then added 10% of additional sample for any bias or loss of data during follow up which concluded total sample size to be at least 200 samples (100 patients each arm).

All women who underwent control-ovarian stimulation (COH) regime using either gonadotrophin combination with GnRH antagonist protocol or mild stimulation protocol using oral letrozole or clomiphene citrate were included in this study. All women underwent follicle tracking by transvaginal ultrasound until dominant follicle size reached (>18mm). IM Ovitrelle (6500 IU) was given and proceed with oocyte retrieval (OR) at least 35-36 hours under transvaginal ultrasonography guidance. The 17-gauge single -lumen needles used for oocyte retrieval under sedation.

ICSI were performed according to local protocol. Zygotes were cultured up to day 5 in G1 medium (Vitrolife). On day 5, embryos were graded according to previously described criteria. One or two embryos were transferred, depending on the morphological score and the developmental stage of the embryo, as well as the age of the patient.

Regardless the ovarian stimulation protocols, these women were assigned into two group; progestogens with additions of GnRH agonist and progestogen only for luteal phase support. Both groups were given routine progestogen support for two weeks duration started from the day of embryo transfer. This includes oral progestogen (Tablet Duphaston 10mg tds), vaginal progestogen (vaginal utrogestan 400mg bd) or intramuscular (IM Proluton 250 mg weekly) as prescribed by attending clinician .

In the first group, there were additional GnRH agonist administrated as a single dose of 0.2 mg decapeptyl given at day 3 after ICSI. The other group with no GnRH agonist given was the control group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 222
• Est. completion date: November 18, 2019
• Est. primary completion date: August 28, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• underwent ICSI

• given progestogens plus GnRH agonist or progestogens only as luteal phase support.

Exclusion Criteria:

• different luteal phase support

• frozen embryo transfer and

• missing medical records data

Related Conditions & MeSH terms

• IVF
• Luteal Phase Defect

Intervention

Drug:
• Decapeptyl 0.2mg
IM Decapeptyl o.2 mg was given 2 days before embryo transfer

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 (24)

Aboulghar MA, Marie H, Amin YM, Aboulghar MM, Nasr A, Serour GI, Mansour RT. GnRH agonist plus vaginal progesterone for luteal phase support in ICSI cycles: a randomized study. Reprod Biomed Online. 2015 Jan;30(1):52-6. doi: 10.1016/j.rbmo.2014.09.017. Ep — View Citation

Ata B, Urman B. Single dose GnRH agonist administration in the luteal phase of assisted reproduction cycles: is the effect dependent on the type of GnRH analogue used for pituitary suppression? Reprod Biomed Online. 2010 Jan;20(1):165-6; author reply 167. — View Citation

Ata B, Yakin K, Balaban B, Urman B. GnRH agonist protocol administration in the luteal phase in ICSI-ET cycles stimulated with the long GnRH agonist protocol: a randomized, controlled double blind study. Hum Reprod. 2008 Mar;23(3):668-73. doi: 10.1093/hum — View Citation

Bar Hava I, Blueshtein M, Ganer Herman H, Omer Y, Ben David G. Gonadotropin-releasing hormone analogue as sole luteal support in antagonist-based assisted reproductive technology cycles. Fertil Steril. 2017 Jan;107(1):130-135.e1. doi: 10.1016/j.fertnstert — View Citation

Beckers NG, Macklon NS, Eijkemans MJ, Ludwig M, Felberbaum RE, Diedrich K, Bustion S, Loumaye E, Fauser BC. Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, — View Citation

Benmachiche A, Benbouhedja S, Zoghmar A, Boularak A, Humaidan P. Impact of Mid-Luteal Phase GnRH Agonist Administration on Reproductive Outcomes in GnRH Agonist-Triggered Cycles: A Randomized Controlled Trial. Front Endocrinol (Lausanne). 2017 Jun 15;8:12 — View Citation

Chen SL, Wu FR, Luo C, Chen X, Shi XY, Zheng HY, Ni YP. Combined analysis of endometrial thickness and pattern in predicting outcome of in vitro fertilization and embryo transfer: a retrospective cohort study. Reprod Biol Endocrinol. 2010 Mar 24;8:30. doi — View Citation

Davar R, Farid Mojtahedi M, Miraj S. Effects of single dose GnRH agonist as luteal support on pregnancy outcome in frozen-thawed embryo transfer cycles: an RCT. Iran J Reprod Med. 2015 Aug;13(8):483-8. — View Citation

Dupont WD, Plummer WD Jr. Power and sample size calculations. A review and computer program. Control Clin Trials. 1990 Apr;11(2):116-28. — View Citation

Fujii S, Sato S, Fukui A, Kimura H, Kasai G, Saito Y. Continuous administration of gonadotrophin-releasing hormone agonist during the luteal phase in IVF. Hum Reprod. 2001 Aug;16(8):1671-5. — View Citation

Isik AZ, Caglar GS, Sozen E, Akarsu C, Tuncay G, Ozbicer T, Vicdan K. Single-dose GnRH agonist administration in the luteal phase of GnRH antagonist cycles: a prospective randomized study. Reprod Biomed Online. 2009 Oct;19(4):472-7. — View Citation

Kolibianakis EM, Bourgain C, Platteau P, Albano C, Van Steirteghem AC, Devroey P. Abnormal endometrial development occurs during the luteal phase of nonsupplemented donor cycles treated with recombinant follicle-stimulating hormone and gonadotropin-releas — View Citation

Kung HF, Chen MJ, Guua HF, Chen YF, Yi YC, Yen-Ping Ho J, Chou MM. Luteal phase support with decapeptyl improves pregnancy outcomes in intracytoplasmic sperm injection with higher basal follicle-stimulating hormone or lower mature oocytes. J Chin Med Asso — View Citation

Pirard C, Donnez J, Loumaye E. GnRH agonist as luteal phase support in assisted reproduction technique cycles: results of a pilot study. Hum Reprod. 2006 Jul;21(7):1894-900. Epub 2006 Mar 23. — View Citation

Pirard C, Donnez J, Loumaye E. GnRH agonist as novel luteal support: results of a randomized, parallel group, feasibility study using intranasal administration of buserelin. Hum Reprod. 2005 Jul;20(7):1798-804. Epub 2005 May 12. — View Citation

Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002 Sep;17(9):2287-99. Review. — View Citation

Qublan H, Amarin Z, Al-Qudah M, Diab F, Nawasreh M, Malkawi S, Balawneh M. Luteal phase support with GnRH-a improves implantation and pregnancy rates in IVF cycles with endometrium of <or=7 mm on day of egg retrieval. Hum Fertil (Camb). 2008 Mar;11(1):43- — View Citation

Razieh DF, Maryam AR, Nasim T. Beneficial effect of luteal-phase gonadotropin-releasing hormone agonist administration on implantation rate after intracytoplasmic sperm injection. Taiwan J Obstet Gynecol. 2009 Sep;48(3):245-8. doi: 10.1016/S1028-4559(09)6 — View Citation

Smitz J, Bourgain C, Van Waesberghe L, Camus M, Devroey P, Van Steirteghem AC. A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation. Hum Repro — View Citation

Tesarik J, Hazout A, Mendoza C. Enhancement of embryo developmental potential by a single administration of GnRH agonist at the time of implantation. Hum Reprod. 2004 May;19(5):1176-80. Epub 2004 Apr 7. — View Citation

Tesarik J, Hazout A, Mendoza-Tesarik R, Mendoza N, Mendoza C. Beneficial effect of luteal-phase GnRH agonist administration on embryo implantation after ICSI in both GnRH agonist- and antagonist-treated ovarian stimulation cycles. Hum Reprod. 2006 Oct;21( — View Citation

Ye H, Luo X, Pei L, Li F, Li C, Chen Y, Zhang X, Huang G. The addition of single dose GnRH agonist to luteal phase support in artificial cycle frozen embryo transfer: a randomized clinical trial. Gynecol Endocrinol. 2019 Jul;35(7):618-622. doi: 10.1080/09 — View Citation

Yildiz GA, Sükür YE, Ates C, Aytaç R. The addition of gonadotrophin releasing hormone agonist to routine luteal phase support in intracytoplasmic sperm injection and embryo transfer cycles: a randomized clinical trial. Eur J Obstet Gynecol Reprod Biol. 20 — View Citation

Zafardoust S, Jeddi-Tehrani M, Akhondi MM, Sadeghi MR, Kamali K, Mokhtar S, Badehnoosh B, Arjmand-Teymouri F, Fatemi F, Mohammadzadeh A. Effect of Administration of Single Dose GnRH Agonist in Luteal Phase on Outcome of ICSI-ET Cycles in Women with Previo — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biochemical pregnancy rate	serum B-HCG more than 5 mIU/ml	14 days after embryo transfer
Primary	clinical pregnancy rate	presence of gestational sac	4 weeks after embryo transfer
Primary	live birth rate	gestation more than 24 weeks	beyond 24 weeks of gestation