The Rescue of Hormonal Replacement Frozen Embryo Transfer Cycle With Low Serum Progesterone.

NCT05758064 | Unknown Phase 2 DMC

• 1 other identifier: 0305825
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

Frozen embryo transfer (FET) is increasingly adopted strategy in modern IVF. Among the many factors that have contributed to such change, the pursuit of an ovarian hyperstimulation syndrome free clinic has been strongly required. Improvements in the vitrification and warming processes and the excellent cryo-survival rates have turned FET in our main tool for preventing this complication. Moreover, a freeze all strategy has proven to provide excellent or even better pregnancy rates (PRs), not only in high but also in normal responders. While ART have rapidly evolved in the areas of embryo culture, vitrification and understanding of the embryo development, little progress has been achieved regarding endometrial preparation for FET. Undoubtedly, correct implantation requires a good quality embryo and a suitable decidualized endometrium. Artificial cycles require hormone replacement treatment (HRT) with estradiol and progesterone (P4). However, there is not a single standardized treatment described for optimal endometrial preparation and no protocol has proven superiority in terms of reproductive outcomes.(5, 6) Although artificial preparation is the most convenient method to schedule FET cycles, recent reports have highlighted a potentially detrimental effect of low P4 levels prior to FET on miscarriage and live birth rates (LBRs). These results have been observed both in homologous and oocyte recipient FET cycles(7, 8), but also in FET cycles of embryos that had undergone PGT for aneuploidies (PGT-A).(9) Additional P4 supplementation may be a way to improve reproductive outcomes in these patients. Our open labelled randomized control study aims to investigate whether patients with low serum P4 levels the day before FET under standard HRT can benefit in terms of clinical and ongoing pregnancy and implantation rates from an individualized luteal phase support consisting in the addition of oral dydrogesterone supplementation or daily subcutaneous P4 injection.

Conditions

Hormonal Replacement Frozen Embryo Transfer Cycle

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy rate

  percentage of cases in which observation of a gestational sac with fetal heart beat by transvaginal ultrasound at 6 weeks of pregnancy

  at the 6 th weeks of pregnancy

Secondary Outcomes (3)

• Serum progesterone level on the day of FET

  on the day of embryo transfer(before transfer)

• Implantation rate

  at the 6 th week of pregnancy

• Ongoing pregnancy rate

  At the 20 th week of gestation

Study Arms (2)

Oral dydrogesterone

ACTIVE COMPARATOR

60 patients in HRT frozen embryo transfer with low serum progesterone less than 10 ng/ml 24 hours before the embryo transfer will be given oral 10 mg dydrogesterone (Duphaston®, Abbott) twice daily

Drug: Duphaston

subcutaneous progesterone

ACTIVE COMPARATOR

60 patients in HRT frozen embryo transfer with low serum progesterone less than 10 ng/ml 24 hours before the embryo transfer will be subcutaneous injection 25mg daily (Prolutex®, IBSA).

Drug: prolutex

Interventions

Duphaston DRUG

10 mg tablet will be given twice

Oral dydrogesterone

prolutex DRUG

subcutaneous injection daily

subcutaneous progesterone

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patient prepared for frozen blastocyst transfer.
• Maternal age ranges from less than 40 years.
• BMI \< 35kg/m2.
• Normal uterine cavity.

You may not qualify if:

• Uncorrected endometrial, uterine or pelvic pathology.
• Recurrent implantation failure cases.
• Patients suffering from recurrent miscarriages.
• Male factor infertility due to azoospermia

Sponsors & Collaborators

• El Shatby University Hospital for Obstetrics and Gynecology: lead

Study Sites (2)

Elshatby University Maternity Hospital

Alexandria, Egypt

RECRUITING

Faculty of Medicine, University of Alexandria

Alexandria, Egypt

RECRUITING

Related Publications (9)

• 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

• Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, Yang J, Liu J, Wei D, Weng N, Tian L, Hao C, Yang D, Zhou F, Shi J, Xu Y, Li J, Yan J, Qin Y, Zhao H, Zhang H, Legro RS. Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome. N Engl J Med. 2016 Aug 11;375(6):523-33. doi: 10.1056/NEJMoa1513873.

  PMID: 27509101 BACKGROUND

• Wei D, Liu JY, Sun Y, Shi Y, Zhang B, Liu JQ, Tan J, Liang X, Cao Y, Wang Z, Qin Y, Zhao H, Zhou Y, Ren H, Hao G, Ling X, Zhao J, Zhang Y, Qi X, Zhang L, Deng X, Chen X, Zhu Y, Wang X, Tian LF, Lv Q, Ma X, Zhang H, Legro RS, Chen ZJ. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019 Mar 30;393(10178):1310-1318. doi: 10.1016/S0140-6736(18)32843-5. Epub 2019 Feb 28.

  PMID: 30827784 BACKGROUND

• Stormlund S, Sopa N, Zedeler A, Bogstad J, Praetorius L, Nielsen HS, Kitlinski ML, Skouby SO, Mikkelsen AL, Spangmose AL, Jeppesen JV, Khatibi A, la Cour Freiesleben N, Ziebe S, Polyzos NP, Bergh C, Humaidan P, Andersen AN, Lossl K, Pinborg A. Freeze-all versus fresh blastocyst transfer strategy during in vitro fertilisation in women with regular menstrual cycles: multicentre randomised controlled trial. BMJ. 2020 Aug 5;370:m2519. doi: 10.1136/bmj.m2519.

  PMID: 32759285 BACKGROUND

• Ghobara T, Gelbaya TA, Ayeleke RO. Cycle regimens for frozen-thawed embryo transfer. Cochrane Database Syst Rev. 2017 Jul 5;7(7):CD003414. doi: 10.1002/14651858.CD003414.pub3.

  PMID: 28675921 BACKGROUND

• Groenewoud ER, Cohlen BJ, Macklon NS. Programming the endometrium for deferred transfer of cryopreserved embryos: hormone replacement versus modified natural cycles. Fertil Steril. 2018 May;109(5):768-774. doi: 10.1016/j.fertnstert.2018.02.135.

  PMID: 29778369 BACKGROUND

• Cedrin-Durnerin I, Isnard T, Mahdjoub S, Sonigo C, Seroka A, Comtet M, Herbemont C, Sifer C, Grynberg M. Serum progesterone concentration and live birth rate in frozen-thawed embryo transfers with hormonally prepared endometrium. Reprod Biomed Online. 2019 Mar;38(3):472-480. doi: 10.1016/j.rbmo.2018.11.026. Epub 2019 Jan 5.

  PMID: 30642638 BACKGROUND

• Volovsky M, Pakes C, Rozen G, Polyakov A. Do serum progesterone levels on day of embryo transfer influence pregnancy outcomes in artificial frozen-thaw cycles? J Assist Reprod Genet. 2020 May;37(5):1129-1135. doi: 10.1007/s10815-020-01713-w. Epub 2020 Feb 10.

  PMID: 32043182 BACKGROUND

• Gaggiotti-Marre S, Martinez F, Coll L, Garcia S, Alvarez M, Parriego M, Barri PN, Polyzos N, Coroleu B. Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates. Gynecol Endocrinol. 2019 May;35(5):439-442. doi: 10.1080/09513590.2018.1534952. Epub 2018 Dec 26.

  PMID: 30585507 BACKGROUND

MeSH Terms

Interventions

Dydrogesterone

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Aly A Hussein, Dr

  University of Alexandria

  STUDY CHAIR

Central Study Contacts

Aly A Hussein, Dr

CONTACT

00201119448000; aly.emam@alexmed.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: March 7, 2023
• Study Start: January 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: December 31, 2023
• Last Updated: March 7, 2023

Record last verified: 2023-03

Locations

EG (2)