AzTrials
AzTrials

InfertilityNCT05716139

Natural Cycle vs Programmed Cycle Frozen Embryo Transfer

A study testing Natural Cycle and Artificial Cycle in people with Infertility and Frozen Embryo Transfer, run by Indira IVF Hospital Pvt Ltd at 1 site in India.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 21 to 45 years, women only
What is being tested?
Natural Cycle and Artificial Cycle
Could I receive a placebo?
No, everyone receives an active treatment
How many people
172 participants
Where
1 siteIndia
Study dates
15 Jul 2023to 26 Mar 2024
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 45 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

India1 site
  • Indira IVF Hospital Private Limited

    Udaipur, Rajasthan, 313001

Other trials in India

About this study

Official title: Preeclampsia Following Natural vs. Artificial Cycle Frozen Embryo Transfer

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

Read more
  • 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.

Read the detailed description

The Research question(PICO) addressed is Does NC-FET decreases the incidence of preeclampsia in patients undergoing frozen embryo transfer as compared to AC-FET . The hypothesis taken is NC-FET will decrease the incidence of preeclampsia compared to AC-FET. The sample size is taken as 3026 (1513 per arm). The Primary 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. The study outcome of the proportion of preeclampsia after 20 weeks of gestation or 6 weeks post-delivery. There are two arms-Arm 1 Active Comparator: Natural Cycle and Arm 2 control: Artificial Cycle FET. The Randomization is done through Random Allocation as per computer generated sequence. The Blinding/masking is done Open labeled. The Study Duration is from Feb 2023 to Jan 2025. Participation Duration is 10 months.

Being tested
Natural Cycle, Artificial Cycle
Keywords
Reproduction, In vitro fertilization, Natural Frozen Embryo Transfer, Artificial Frozen Embryo Transfer, Preeclampsia
Medical subject headings
Infertility, Pre-Eclampsia, Eclampsia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Natural CycleProcedure or surgery

    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.

  • Artificial CycleProcedure or surgery

    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.

Study groups in NCT05716139
Study groupRoleWhat they receive
Natural CycleActive comparatorIn this,hCG trigger and Luteal Phase Support is monitored for the natural frozen embryo cycle procedure of IVF.
Receives: Procedure: Natural Cycle
Artificial CycleOtherIn this, endometrial preparation and Luteal Phase Support is monitored for the artificial frozen embryo cycle procedure of IVF.
Receives: Procedure: Artificial Cycle

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (17)
  1. Biochemical Pregnancy Rate

    Pregnancies diagnosed only by β-human chorionic gonadotropin detection without a gestational sac visualized by vaginal ultrasound at the 6th gestational week.

    Measured: 6 weeks after Embryo Transfer

  2. Implantation Rate

    The number of gestational sacs observed by transvaginal ultrasound at the 6th gestational week per the number of embryos transferred.

    Measured: 4 weeks +2 weeks after ET

  3. Clinical Pregnancy Rate

    Detection of a foetal heartbeat on transvaginal ultrasound at the 6th gestational week per embryo transfer cycle.

    Measured: 4 weeks +2 weeks after ET

  4. Ongoing Pregnancy Rate

    Presence of gestational sacs with a heartbeat at the 12th gestational week per embryo transfer cycle.

    Measured: 12 weeks after embryo Transfer

  5. Live Birth Rate

    The number of deliveries that resulted in at least one live birth per 100 Embryo transferred cycle.

    Measured: 28 weeks(+12 weeks) after embryo transfer

  6. Miscarriage Rate

    Number of spontaneous pregnancy losses in which a gestational sac/s was previously observed (before 20th gestational weeks) per 100 clinical pregnancy.

    Measured: Within 20 weeks of gestation

  7. Preterm birth

    Preterm is defined as babies born alive before 37 weeks of pregnancy are completed

    Measured: < 37 weeks

  8. Extreme preterm birth

    Extreme Preterm is defined as babies born alive before 28 weeks of pregnancy

    Measured: 20-28 weeks

  9. Fetal growth restriction

    Fetal growth restriction (FGR) is most often defined as an estimated fetal weight less than the 10th percentile for gestational age by prenatal ultrasound evaluation

    Measured: 20-40 weeks of gestation

  10. Fetal birthweight

    Is defined as the weight of baby just after birth

    Measured: within 30 minutes of birth

  11. Premature detachment of normally inserted placenta

    It is defined as a premature separation of the placenta before delivery.

    Measured: 12 weeks of GA till labor

  12. Maternal hypertension

    It is defined as blood pressure more than 140/90 mm Hg detected first time after 20 weeks of gestation till 6 weeks of postpartum without proteinuria

    Measured: After 20 weeks of GA till 6 weeks postpartum

  13. Eclampsia

    Eclampsia is defined as the new onset of generalized tonic-clonic seizures in a woman with preeclampsia.

    Measured: After 20 weeks of GA till 6 weeks postpartum

  14. HELLP Syndrome

    It is defined as hemodialysis, elevated liver enzymes, and low platelet count

    Measured: After 20 weeks of GA till 6 weeks postpartum

  15. Maternal mortality

    Maternal death is defined as pregnancy or its management (excluding accidental or incidental causes) during pregnancy and childbirth or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy

    Measured: from start of pregnancy to 42 weeks of pregnancy

  16. Fetal death

    Fetal death refers to the spontaneous intrauterine death of a fetus after 20 weeks of GA before delivery

    Measured: 20 weeks of GA before delivery

  17. Frequency of adverse events

    An adverse event (AE) is any untoward medical occurrence in a patient.

    Measured: through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2023
  2. Study start15 Jul 2023
  3. Primary completion26 Mar 2024
  4. Study completion26 Mar 2024

Why it stopped: As per institutional protocol unable to recruit adequate amount of participants

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open labelled parallel group randomized Controlled Trial
Masking
None (open label)
Enrolment
172 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05716139
Sponsor's protocol ID
IIHPL-UDR/RCT/013_2022
Status last verified
Jul 2023
First submitted
21 Jan 2023
Last updated
3 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: IPD will be shared with other researchers after publication of primary results.

Publications

  • 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.

    PubMed 30910545
  • 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.

    PubMed 27548556
  • 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.

    PubMed 34579768
  • 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.

    PubMed 35553678
  • 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.

    PubMed 21828116
  • 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.

    PubMed 30095760
  • 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.

    PubMed 35227270
  • 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.

    PubMed 28322775
  • 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.

    PubMed 30825923
  • 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.

    PubMed 27827818
  • 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.

    PubMed 30636552
  • 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.

    PubMed 22051447
  • 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.

    PubMed 29320646

Questions about this trial

What is this clinical trial studying?

A study testing Natural Cycle and Artificial Cycle in people with Infertility and Frozen Embryo Transfer, run by Indira IVF Hospital Pvt Ltd at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early (reason given: As per institutional protocol unable to recruit adequate amount of participants). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

proportion of preeclampsia (time frame: after the 20th week of gestation up to six weeks postpartum). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05716139, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2025.

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