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Natural Cycle vs Programmed Cycle Frozen Embryo Transfer

Primary Purpose

Infertility, Frozen Embryo Transfer, Preeclampsia and Eclampsia

Status
Recruiting
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Natural Cycle
Artificial Cycle
Sponsored by
Indira IVF Hospital Pvt Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility focused on measuring Reproduction, In vitro fertilization, Natural Frozen Embryo Transfer, Artificial Frozen Embryo Transfer, Preeclampsia

Eligibility Criteria

21 Years - 45 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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

Sites / Locations

  • Indira IVF Hospital Private LimitedRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Other

Arm Label

Natural Cycle

Artificial Cycle

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Implantation Rate
The number of gestational sacs observed by transvaginal ultrasound at the 6th gestational week per the number of embryos transferred.
Clinical Pregnancy Rate
Detection of a foetal heartbeat on transvaginal ultrasound at the 6th gestational week per embryo transfer cycle.
Ongoing Pregnancy Rate
Presence of gestational sacs with a heartbeat at the 12th gestational week per embryo transfer cycle.
Live Birth Rate
The number of deliveries that resulted in at least one live birth per 100 Embryo transferred cycle.
Miscarriage Rate
Number of spontaneous pregnancy losses in which a gestational sac/s was previously observed (before 20th gestational weeks) per 100 clinical pregnancy.
Preterm birth
Preterm is defined as babies born alive before 37 weeks of pregnancy are completed
Extreme preterm birth
Extreme Preterm is defined as babies born alive before 28 weeks of pregnancy
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
Fetal birthweight
Is defined as the weight of baby just after birth
Premature detachment of normally inserted placenta
It is defined as a premature separation of the placenta before delivery.
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
Eclampsia
Eclampsia is defined as the new onset of generalized tonic-clonic seizures in a woman with preeclampsia.
HELLP Syndrome
It is defined as hemodialysis, elevated liver enzymes, and low platelet count
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
Fetal death
Fetal death refers to the spontaneous intrauterine death of a fetus after 20 weeks of GA before delivery
Frequency of adverse events
An adverse event (AE) is any untoward medical occurrence in a patient.

Full Information

First Posted
January 21, 2023
Last Updated
July 29, 2023
Sponsor
Indira IVF Hospital Pvt Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05716139
Brief Title
Natural Cycle vs Programmed Cycle Frozen Embryo Transfer
Official Title
Preeclampsia Following Natural vs. Artificial Cycle Frozen Embryo Transfer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 15, 2023 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indira IVF Hospital Pvt Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Frozen Embryo Transfer, Preeclampsia and Eclampsia
Keywords
Reproduction, In vitro fertilization, Natural Frozen Embryo Transfer, Artificial Frozen Embryo Transfer, Preeclampsia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Open labelled parallel group randomized Controlled Trial
Masking
None (Open Label)
Masking Description
Parallel group open labelled masking
Allocation
Randomized
Enrollment
3026 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Natural Cycle
Arm Type
Active Comparator
Arm Description
In this,hCG trigger and Luteal Phase Support is monitored for the natural frozen embryo cycle procedure of IVF.
Arm Title
Artificial Cycle
Arm Type
Other
Arm Description
In this, endometrial preparation and Luteal Phase Support is monitored for the artificial frozen embryo cycle procedure of IVF.
Intervention Type
Procedure
Intervention Name(s)
Natural Cycle
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Artificial Cycle
Intervention Description
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.
Primary Outcome Measure Information:
Title
proportion of preeclampsia
Description
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.
Time Frame
after the 20th week of gestation up to six weeks postpartum
Secondary Outcome Measure Information:
Title
Biochemical Pregnancy Rate
Description
Pregnancies diagnosed only by β-human chorionic gonadotropin detection without a gestational sac visualized by vaginal ultrasound at the 6th gestational week.
Time Frame
6 weeks after Embryo Transfer
Title
Implantation Rate
Description
The number of gestational sacs observed by transvaginal ultrasound at the 6th gestational week per the number of embryos transferred.
Time Frame
4 weeks +2 weeks after ET
Title
Clinical Pregnancy Rate
Description
Detection of a foetal heartbeat on transvaginal ultrasound at the 6th gestational week per embryo transfer cycle.
Time Frame
4 weeks +2 weeks after ET
Title
Ongoing Pregnancy Rate
Description
Presence of gestational sacs with a heartbeat at the 12th gestational week per embryo transfer cycle.
Time Frame
12 weeks after embryo Transfer
Title
Live Birth Rate
Description
The number of deliveries that resulted in at least one live birth per 100 Embryo transferred cycle.
Time Frame
28 weeks(+12 weeks) after embryo transfer
Title
Miscarriage Rate
Description
Number of spontaneous pregnancy losses in which a gestational sac/s was previously observed (before 20th gestational weeks) per 100 clinical pregnancy.
Time Frame
Within 20 weeks of gestation
Title
Preterm birth
Description
Preterm is defined as babies born alive before 37 weeks of pregnancy are completed
Time Frame
< 37 weeks
Title
Extreme preterm birth
Description
Extreme Preterm is defined as babies born alive before 28 weeks of pregnancy
Time Frame
20-28 weeks
Title
Fetal growth restriction
Description
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
Time Frame
20-40 weeks of gestation
Title
Fetal birthweight
Description
Is defined as the weight of baby just after birth
Time Frame
within 30 minutes of birth
Title
Premature detachment of normally inserted placenta
Description
It is defined as a premature separation of the placenta before delivery.
Time Frame
12 weeks of GA till labor
Title
Maternal hypertension
Description
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
Time Frame
After 20 weeks of GA till 6 weeks postpartum
Title
Eclampsia
Description
Eclampsia is defined as the new onset of generalized tonic-clonic seizures in a woman with preeclampsia.
Time Frame
After 20 weeks of GA till 6 weeks postpartum
Title
HELLP Syndrome
Description
It is defined as hemodialysis, elevated liver enzymes, and low platelet count
Time Frame
After 20 weeks of GA till 6 weeks postpartum
Title
Maternal mortality
Description
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
Time Frame
from start of pregnancy to 42 weeks of pregnancy
Title
Fetal death
Description
Fetal death refers to the spontaneous intrauterine death of a fetus after 20 weeks of GA before delivery
Time Frame
20 weeks of GA before delivery
Title
Frequency of adverse events
Description
An adverse event (AE) is any untoward medical occurrence in a patient.
Time Frame
through study completion, an average of 1 year

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Female
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nikolaos P. Polyzos, MD
Phone
+34 932274896
Email
nikpol@dexeus.com
First Name & Middle Initial & Last Name or Official Title & Degree
Nihar Ranjan Bhoi, MD
Phone
+91 7205783512
Email
drnihar.bhoi@indiraivf.in
Facility Information:
Facility Name
Indira IVF Hospital Private Limited
City
Udaipur
State/Province
Rajasthan
ZIP/Postal Code
313001
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vipin Chandra, DGO
Phone
+91 9567971239
Email
ifa@indiraivf.in
First Name & Middle Initial & Last Name & Degree
Nihar R Bhoi, MD
Phone
+91 7205783512
Email
drnihar.bhoi@indira.ivf.in
First Name & Middle Initial & Last Name & Degree
Nihar R Bhoi, MD
First Name & Middle Initial & Last Name & Degree
Anuja Singh, MD
First Name & Middle Initial & Last Name & Degree
Shyam Gupta, MD
First Name & Middle Initial & Last Name & Degree
Ritu Punhani, MD
First Name & Middle Initial & Last Name & Degree
Anjali Gahlan, MD
First Name & Middle Initial & Last Name & Degree
Amol Wankhede, MS
First Name & Middle Initial & Last Name & Degree
Amol Lukund, MD
First Name & Middle Initial & Last Name & Degree
Akanksha Jangid, MD
First Name & Middle Initial & Last Name & Degree
Amrita Singh, MS

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD will be shared with other researchers after publication of primary results.
IPD Sharing Time Frame
After six months of publication of primary results statistical plan and ICF
IPD Sharing Access Criteria
IPD will be shared on request
Citations:
PubMed Identifier
30910545
Citation
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.
Results Reference
background
PubMed Identifier
27548556
Citation
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.
Results Reference
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PubMed Identifier
34579768
Citation
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.
Results Reference
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PubMed Identifier
35553678
Citation
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.
Results Reference
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21828116
Citation
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.
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30095760
Citation
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.
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Citation
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.
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Natural Cycle vs Programmed Cycle Frozen Embryo Transfer

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