Natural Cycle vs Programmed Cycle Frozen Embryo Transfer

NCT05716139 | Terminated DMC

• 1 other identifier: IIHPL-UDR/RCT/013_2022
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this\[ type of study: randomized controlled trial\]is to compare Preeclampsia following Natural vs. Artificial Cycle in patients undergoing frozen embryo transfer. The main question\[s\] it aims to answer is • Does NC-FET decreases the incidence of preeclampsia in patients undergoing frozen embryo transfer as compared to AC-FET ? The main objective is to compare the proportion of preeclampsia in women with a viable pregnancy with natural cycle protocol to artificial cycle protocol when practicing frozen embryo transfer. Participants recruited will be divided into two ARM(1513 per arm). ARM 1 will undergo the Natural Cycle procedure of Embryo transfer, and ARM 2 will undergo the Artificial Cycle procedure of Embryo transfer. The primary outcome will be the proportion of preeclampsia. The duration of the study is around 2 year.

Conditions

Infertility; Frozen Embryo Transfer; Preeclampsia and Eclampsia

Keywords

Reproduction; In vitro fertilization; Natural Frozen Embryo Transfer; Artificial Frozen Embryo Transfer; Preeclampsia

Outcome Measures

Primary Outcomes (1)

• proportion of preeclampsia

  The primary efficacy endpoint is the proportion of preeclampsia in women assigned to a natural cycle protocol compared to the proportion of preeclampsia in women assigned to an artificial cycle protocol.

  after the 20th week of gestation up to six weeks postpartum

Secondary Outcomes (17)

• Biochemical Pregnancy Rate

  6 weeks after Embryo Transfer

• Implantation Rate

  4 weeks +2 weeks after ET

• Clinical Pregnancy Rate

  4 weeks +2 weeks after ET

• Ongoing Pregnancy Rate

  12 weeks after embryo Transfer

• Live Birth Rate

  28 weeks(+12 weeks) after embryo transfer

Study Arms (2)

Natural Cycle

ACTIVE COMPARATOR

In this,hCG trigger and Luteal Phase Support is monitored for the natural frozen embryo cycle procedure of IVF.

Procedure: Natural Cycle

Artificial Cycle

OTHER

In this, endometrial preparation and Luteal Phase Support is monitored for the artificial frozen embryo cycle procedure of IVF.

Procedure: Artificial Cycle

Interventions

Natural Cycle PROCEDURE

The participant will be administered a S/C injection of 250mcg r-hCG to assist ovulation and timing of the embryo transfer, when the dominant follicle reaches ≥ 18mm and serum LH \< 20 IU/L, the administration of r-hCG will be in the evening, and the embryo transfer will be scheduled seven days later (window of ± two days). The participant will begin transvaginal progesterone gel (8 %) twice daily starting 36 hrs after the trigger until ten weeks of gestation.

Natural Cycle

Artificial Cycle PROCEDURE

Estrogen priming with oral estradiol valerate 6mg/day (2mg every 8 hours) starting from cycle D1-D5 after a first TVU. TVU will be performed 10-15 days after beginning estradiol until ET ≥ 7mm, maximum until 21 days. Patients will begin progesterone injection 100mg/day until blastocyst transfer. Frozen embryo transfer will be performed on day 6 +/- 2 days of progesterone administration. After embryo transfer, a supplementation with transvaginal progesterone gel (8 %) twice daily starting from the day of embryo transfer until ten weeks of gestation. Patients will continue Estradiol 2 mg thrice daily until 6 weeks of gestation; then dose tapering will be done to 2 mg twice daily until 9 wks of gestation. From 9th wk the estrogen dose will be tapered further to 2 mg once daily for 10 days before stopping.

Artificial Cycle

Eligibility Criteria

• Age: 21 Years - 45 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Endometrial preparation with Hormone replacement therapy/ Natural cycle.
• Age 21-45 years following an autologous IVF cycle (with or without preimplantation genetic testing for aneuploidy)
• BMI \> 18 and \< 30 kg/m2
• Endometrial thickness ≥ 7 mm after estrogen therapy or on the day of ovulation
• Blastocyst embryo transfer

You may not qualify if:

• Uterine diseases (e.g. submucosal fibroids, polyps, previously diagnosed Müllerian abnormalities)
• Hydrosalpinx untreated.
• Recurrent pregnancy loss (≥ 3 previous miscarriages)
• Recurrent implantation failure (≥ 3 previously failed embryo transfers of good-quality blastocysts)
• Allergy to study medication
• Pregnancy or lactation at recruitment
• Contraindications for hormonal treatment

Sponsors & Collaborators

• Indira IVF Hospital Pvt Ltd: lead

Study Sites (1)

Indira IVF Hospital Private Limited

Udaipur, Rajasthan, 313001, India

Location

Related Publications (13)

• American College of Obstetricians and Gynecologists' Committee on Obstetric Practice; Committee on Genetics; U.S. Food and Drug Administration. Committee Opinion No 671: Perinatal Risks Associated With Assisted Reproductive Technology. Obstet Gynecol. 2016 Sep;128(3):e61-8. doi: 10.1097/AOG.0000000000001643.

  PMID: 27548556 BACKGROUND

• Baksh S, Casper A, Christianson MS, Devine K, Doody KJ, Ehrhardt S, Hansen KR, Lathi RB, Timbo F, Usadi R, Vitek W, Shade DM, Segars J, Baker VL; NatPro Study Group. Natural vs. programmed cycles for frozen embryo transfer: study protocol for an investigator-initiated, randomized, controlled, multicenter clinical trial. Trials. 2021 Sep 27;22(1):660. doi: 10.1186/s13063-021-05637-3.

  PMID: 34579768 BACKGROUND

• Busnelli A, Schirripa I, Fedele F, Bulfoni A, Levi-Setti PE. Obstetric and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis. Hum Reprod. 2022 Jun 30;37(7):1619-1641. doi: 10.1093/humrep/deac073.

  PMID: 35553678 BACKGROUND

• Devroey P, Polyzos NP, Blockeel C. An OHSS-Free Clinic by segmentation of IVF treatment. Hum Reprod. 2011 Oct;26(10):2593-7. doi: 10.1093/humrep/der251. Epub 2011 Aug 9.

  PMID: 21828116 BACKGROUND

• Ginstrom Ernstad E, Wennerholm UB, Khatibi A, Petzold M, Bergh C. Neonatal and maternal outcome after frozen embryo transfer: Increased risks in programmed cycles. Am J Obstet Gynecol. 2019 Aug;221(2):126.e1-126.e18. doi: 10.1016/j.ajog.2019.03.010. Epub 2019 Mar 22.

  PMID: 30910545 BACKGROUND

• Kawwass JF, Badell ML. Maternal and Fetal Risk Associated With Assisted Reproductive Technology. Obstet Gynecol. 2018 Sep;132(3):763-772. doi: 10.1097/AOG.0000000000002786.

  PMID: 30095760 BACKGROUND

• Lee JC, Badell ML, Kawwass JF. The impact of endometrial preparation for frozen embryo transfer on maternal and neonatal outcomes: a review. Reprod Biol Endocrinol. 2022 Feb 28;20(1):40. doi: 10.1186/s12958-021-00869-z.

  PMID: 35227270 BACKGROUND

• Luke B. Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies. Am J Obstet Gynecol. 2017 Sep;217(3):270-281. doi: 10.1016/j.ajog.2017.03.012. Epub 2017 Mar 18.

  PMID: 28322775 BACKGROUND

• Malik A, Jee B, Gupta SK. Preeclampsia: Disease biology and burden, its management strategies with reference to India. Pregnancy Hypertens. 2019 Jan;15:23-31. doi: 10.1016/j.preghy.2018.10.011. Epub 2018 Nov 2.

  PMID: 30825923 BACKGROUND

• Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM, Vanderpoel S, Racowsky C. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update. 2017 Mar 1;23(2):139-155. doi: 10.1093/humupd/dmw038.

  PMID: 27827818 BACKGROUND

• von Versen-Hoynck F, Schaub AM, Chi YY, Chiu KH, Liu J, Lingis M, Stan Williams R, Rhoton-Vlasak A, Nichols WW, Fleischmann RR, Zhang W, Winn VD, Segal MS, Conrad KP, Baker VL. Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum. Hypertension. 2019 Mar;73(3):640-649. doi: 10.1161/HYPERTENSIONAHA.118.12043.

  PMID: 30636552 BACKGROUND

• Chen JZ, Sheehan PM, Brennecke SP, Keogh RJ. Vessel remodelling, pregnancy hormones and extravillous trophoblast function. Mol Cell Endocrinol. 2012 Feb 26;349(2):138-44. doi: 10.1016/j.mce.2011.10.014. Epub 2011 Oct 25.

  PMID: 22051447 BACKGROUND

• Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, Zhu Y, Deng X, Qi X, Li H, Ma X, Ren H, Wang Y, Zhang D, Wang B, Liu F, Wu Q, Wang Z, Bai H, Li Y, Zhou Y, Sun M, Liu H, Li J, Zhang L, Chen X, Zhang S, Sun X, Legro RS, Chen ZJ. Transfer of Fresh versus Frozen Embryos in Ovulatory Women. N Engl J Med. 2018 Jan 11;378(2):126-136. doi: 10.1056/NEJMoa1705334.

  PMID: 29320646 BACKGROUND

MeSH Terms

Conditions

Infertility; Pre-Eclampsia; Eclampsia

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Parallel group open labelled masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open labelled parallel group randomized Controlled Trial

Study Record Dates

• First Submitted: January 21, 2023
• First Posted: February 8, 2023
• Study Start: July 15, 2023
• Primary Completion: March 26, 2024
• Study Completion: March 26, 2024
• Last Updated: April 3, 2025

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After six months of publication of primary results statistical plan and ICF
• Access Criteria: IPD will be shared on request

Locations

IN (1)