Effect of Intramuscular Progesterone Supplementation on Clinical and Ongoing Pregnancy Rates in Patients With Low Serum Progesterone Levels on the Day of Embryo Transfer in Artificial Frozen Cycles

NCT04837768 | Completed

• 1 other identifier: Progesterone in HRT FET cycles
• Study Type: interventional
• Target: 354
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of this study is to investigate whether intramuscular progesterone supplementation will improve clinical pregnancy rates and ongoing pregnancy rates in patients with decreased serum progesterone levels on the day of embryo transfer in artificial frozen cycles.

Conditions

Serum Progesterone Levels; Progesterone Supplementation; Frozen Embryo Transfer; Clinical Pregnancy Rates; Ongoing Pregnancy Rates

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy rates

  Detected via ultrasound

  4 weeks after the day of embryo transfer

Secondary Outcomes (1)

• Ongoing pregnancy rates

  12 weeks after the day of embryo transfer

Study Arms (2)

Serum Progesterone Levels >9.2 ng/ml

ACTIVE COMPARATOR

These patients will receive only twice-daily vaginal progesterone supplementation following embryo transfer

Drug: Twice-daily transvaginal progesterone supplementation

Serum Progesterone Levels <9.2 ng/ml

ACTIVE COMPARATOR

These patients will receive twice-weekly intramuscular progesterone supplementation in addition to the twice-daily vaginal supplementation following embryo transfer

Drug: Twice-weekly intramuscular + Twice-daily transvaginal progesterone supplementation

Interventions

Twice-daily transvaginal progesterone supplementation DRUG

Patients with serum progesterone levels \>9.2 ng/ml on the day of embryo transfer in artificial frozen cycles will receive the traditional twice-daily vaginal progesterone supplementation till 12 weeks gestation.

Serum Progesterone Levels >9.2 ng/ml

Twice-weekly intramuscular + Twice-daily transvaginal progesterone supplementation DRUG

Patients with serum progesterone levels \<9.2 ng/ml on the day of embryo transfer in artificial frozen cycles will receive the twice-daily vaginal progesterone in addition to twice-weekly intramuscular progesterone supplementation till 12 weeks gestation.

Serum Progesterone Levels <9.2 ng/ml

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age range 20-40 years
• BMI \< 40 kg/m2
• Endometrial thickness \>7mm
• Double embryo transfer (Day 5), Grade 1 or 2.

You may not qualify if:

• Autoimmune diseases
• Uncontrolled medical conditions
• Recurrent implantation failure
• Anatomical uterine abnormalities as polyps, fibroids or Müllerian anomalies.

Sponsors & Collaborators

• Cairo University: lead

Study Sites (2)

Cairo University, Faculty of Medicine, Department of Obstetrics and Gynecology

Cairo, 11956, Egypt

Location

AlBoshra IVF & Infertility Treatment Centre

Cairo, 12611, Egypt

Location

Related Publications (7)

• Labarta E, Mariani G, Holtmann N, Celada P, Remohi J, Bosch E. Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Hum Reprod. 2017 Dec 1;32(12):2437-2442. doi: 10.1093/humrep/dex316.

  PMID: 29040638 BACKGROUND

• Boynukalin FK, Gultomruk M, Turgut E, Demir B, Findikli N, Serdarogullari M, Coban O, Yarkiner Z, Bahceci M. Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers. Reprod Biol Endocrinol. 2019 Nov 29;17(1):102. doi: 10.1186/s12958-019-0549-9.

  PMID: 31783865 BACKGROUND

• Kofinas JD, Blakemore J, McCulloh DH, Grifo J. Serum progesterone levels greater than 20 ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates. J Assist Reprod Genet. 2015 Sep;32(9):1395-9. doi: 10.1007/s10815-015-0546-7. Epub 2015 Aug 4.

  PMID: 26238390 BACKGROUND

• Yovich JL, Conceicao JL, Stanger JD, Hinchliffe PM, Keane KN. Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement. Reprod Biomed Online. 2015 Aug;31(2):180-91. doi: 10.1016/j.rbmo.2015.05.005. Epub 2015 May 18.

  PMID: 26099447 BACKGROUND

• Mackens S, Santos-Ribeiro S, van de Vijver A, Racca A, Van Landuyt L, Tournaye H, Blockeel C. Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Hum Reprod. 2017 Nov 1;32(11):2234-2242. doi: 10.1093/humrep/dex285.

  PMID: 29025055 BACKGROUND

• Shapiro DB, Pappadakis JA, Ellsworth NM, Hait HI, Nagy ZP. Progesterone replacement with vaginal gel versus i.m. injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod. 2014 Aug;29(8):1706-11. doi: 10.1093/humrep/deu121. Epub 2014 May 20.

  PMID: 24847018 BACKGROUND

• Paulson RJ, Collins MG, Yankov VI. Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert. J Clin Endocrinol Metab. 2014 Nov;99(11):4241-9. doi: 10.1210/jc.2013-3937. Epub 2014 Feb 25.

  PMID: 24606090 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer in the Department of Obstetrics and Gynecology

Model Details: Patients undergoing frozen cycles following ICSI will receive artificial endometrial preparation from day 2/3 of their cycle in the form of 2mg Estradiol Valerate pills thrice daily for 7-10 days. After confirming endometrial thickness \> 7mm via TVS, progesterone supplementation will start via Prontogest® 400mg vaginal pessaries twice daily for 5 days, ending with the day of embryo transfer (ET). On the morning of ET, serum progesterone will be measured and if the value is over 9.2ng/ml, only the traditional twice daily vaginal progesterone will be resumed until 12 weeks gestation. If the value is under 9.2 ng/ml, intramuscular progesterone supplementation with Prontogest® 100mg will be added in twice-weekly doses (every 3 days) to the vaginal supplementation. Quantitative β-hcg 2 weeks after ET to detect chemical pregnancies. Ultrasound 4 weeks after ET to detect clinical pregnancies. Ultrasound repeated at 12 weeks to confirm ongoing pregnancy rates.

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 8, 2021
• Study Start: July 27, 2021
• Primary Completion: March 1, 2022
• Study Completion: March 15, 2022
• Last Updated: March 17, 2022

Record last verified: 2022-03

Locations

EG (2)