Clinical trial NCT04454749: Endometrial Compaction and Its Influence on Pregnancy Rate in Frozen Embryo Cycle Regimes
Official title: Endometrial Compaction and Its Influence on Pregnancy Rate in Frozen Embryo Cycle Regimes
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Endometrial Disorder
Infertility, Female
IVF
Pregnancy Early
Keywords: infertilty
progesterone
endometrium
pregnancy
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2020-07-01
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients who are undergoing ovarian stimulation for IVF/ICSI with pre-implantation genetic screening and embryo vitrification, who are planned for their first FET transfer cycle.

Brief summary: For a pregnancy to occur, an euploid embryo at blastocyst developmental stage, a receptive endometrium and the synchrony of both is crucial. Many studies lately investigated the influence of the endometrial thickness and pattern on the artificial reproductive technology (ART) outcome, however, with conflicting results.

Detailed description: Further on, the measurement of the endometrial thickness was mostly performed either on the day of final oocyte maturation in stimulated cycles with fresh embryo transfer or on the day of progesterone administration in FET cycles.

Progesterone is essential for the secretory transformation and compaction of the endometrium, prior to implantation. A recently published paper (Haas et al., 2019) however, evaluated the degree of endometrial compaction under the influence of progesterone in FET cycles and described, that a lack of certain endometrial compaction has a negative impact on the ongoing pregnancy rate. As in this study embryos of unknown ploidy status were transferred, the role of embryo ploidy on the outcome may bias the study results.

In the herein presented study protocol we aim to investigate the influence of endometrial compaction in FET cycles in which euploid embryos are transferred.

HYPOTHESIS: Lack of endometrial compaction after the start of progesterone leads to an impaired reproductive outcome.

Eligibility criteria: Inclusion Criteria:

* Women aged 18 years to 40 years with regular menses (26-34 days)
* Having 1 or 2 chromosomally normal cryopreserved blastocysts available for transfer after IVF / ICSI treatment
* First frozen-thawed transfer cycle
* Progesterone level \< 1.5 ng/mL day of trigger injection in stimulation cycle from which embryos to be transferred were created.

Exclusion Criteria:

* Polycystic ovarian syndrome
* Poor ovarian responder in accordance with Bologna criteria
* Uterine abnormality US / saline infusion sonohysterogram
* Previous dilatation \& curettage (D\&C)
* Hydrosalpinx
* Asherman syndrome
* History of endometriosis AFS ≥ 2
* ICSI due to severe male factor with testicular sperm
* Any known contraindications or allergy to oral estradiol or progesterone.
* Discontinuation of HRT medication ( medication error in research HRT cycle )
* Failure to detect ovulation in the research natural cycle
* Ovulation after day 20 in a natural cycle
* Duration of estradiol exposure ≥ 17 days and endometrium \< 6mm
* Spontaneous ovulation in HRT artificial cycle

Primary outcomes:
measure: Ongoing pregnancy rate
timeFrame: 12 weeks
Secondary outcomes:
measure: Biochemical pregnancy rate in HRT cycle
timeFrame: 5 weeks
measure: Biochemical pregnancy rate in spontaneous cycle
timeFrame: 5 weeks
measure: Clinical implantation rate in HRT cycle
timeFrame: 6 weeks
measure: Clinical implantation rate in spontaneous cycle
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: IVI Middle East Fertility Clinic
Study officials:
affiliation: IVI Middle East Fertility Clinic LLC
name: Barbara Lawrenz, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bu Z, Sun Y. The Impact of Endometrial Thickness on the Day of Human Chorionic Gonadotrophin (hCG) Administration on Ongoing Pregnancy Rate in Patients with Different Ovarian Response. PLoS One. 2015 Dec 30;10(12):e0145703. doi: 10.1371/journal.pone.0145703. eCollection 2015.
citation: Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25.
citation: Haas J, Smith R, Zilberberg E, Nayot D, Meriano J, Barzilay E, Casper RF. Endometrial compaction (decreased thickness) in response to progesterone results in optimal pregnancy outcome in frozen-thawed embryo transfers. Fertil Steril. 2019 Sep;112(3):503-509.e1. doi: 10.1016/j.fertnstert.2019.05.001. Epub 2019 Jun 24.
citation: Irani M, Robles A, Gunnala V, Reichman D, Rosenwaks Z. Optimal parameters for determining the LH surge in natural cycle frozen-thawed embryo transfers. J Ovarian Res. 2017 Oct 16;10(1):70. doi: 10.1186/s13048-017-0367-7.
citation: Kasius A, Smit JG, Torrance HL, Eijkemans MJ, Mol BW, Opmeer BC, Broekmans FJ. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update. 2014 Jul-Aug;20(4):530-41. doi: 10.1093/humupd/dmu011. Epub 2014 Mar 23.
citation: La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update. 2014 Jan-Feb;20(1):124-40. doi: 10.1093/humupd/dmt037. Epub 2013 Sep 29.
citation: Lawrenz B, Labarta E, Fatemi H, Bosch E. Premature progesterone elevation: targets and rescue strategies. Fertil Steril. 2018 Apr;109(4):577-582. doi: 10.1016/j.fertnstert.2018.02.128.
citation: Liu KE, Hartman M, Hartman A, Luo ZC, Mahutte N. The impact of a thin endometrial lining on fresh and frozen-thaw IVF outcomes: an analysis of over 40 000 embryo transfers. Hum Reprod. 2018 Oct 1;33(10):1883-1888. doi: 10.1093/humrep/dey281.
citation: Liu Y, Ye XY, Chan C. The association between endometrial thickness and pregnancy outcome in gonadotropin-stimulated intrauterine insemination cycles. Reprod Biol Endocrinol. 2019 Jan 23;17(1):14. doi: 10.1186/s12958-019-0455-1.
citation: Testart J, Frydman R, Feinstein MC, Thebault A, Roger M, Scholler R. Interpretation of plasma luteinizing hormone assay for the collection of mature oocytes from women: definition of a luteinizing hormone surge-initiating rise. Fertil Steril. 1981 Jul;36(1):50-4. doi: 10.1016/s0015-0282(16)45617-7.
citation: Vaegter KK, Lakic TG, Olovsson M, Berglund L, Brodin T, Holte J. Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers. Fertil Steril. 2017 Mar;107(3):641-648.e2. doi: 10.1016/j.fertnstert.2016.12.005. Epub 2017 Jan 17.
citation: Yuan X, Saravelos SH, Wang Q, Xu Y, Li TC, Zhou C. Endometrial thickness as a predictor of pregnancy outcomes in 10787 fresh IVF-ICSI cycles. Reprod Biomed Online. 2016 Aug;33(2):197-205. doi: 10.1016/j.rbmo.2016.05.002. Epub 2016 May 13.
citation: Zhao J, Zhang Q, Wang Y, Li Y. Endometrial pattern, thickness and growth in predicting pregnancy outcome following 3319 IVF cycle. Reprod Biomed Online. 2014 Sep;29(3):291-8. doi: 10.1016/j.rbmo.2014.05.011. Epub 2014 Jun 13.