Comparison of Day 19 and Day 20 Artificial FET

NCT ID: NCT02788097

Last Updated: 2017-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2016-10-31

Brief Summary

In recent artificial frozen embryo transfers (FET) in which blastocysts vitrified on day 4 of culture and transferred on P+4, with blastocysts traditionally transferred on P+5, a high rate of implantation has been observed. In addition, a greater number of these implantations resulted in clinical pregnancies (i.e., a conceptus with normal fetal heart activity). In this prospective randomised control study, the investigators will investigate whether this increased viability, is due either to embryo quality, endometrial receptivity, or a combination of the two factors by randomizing the transfer of day 5 blastocysts to P+4 or P+5.

Detailed Description

During the first 20 years of IVF embryo transfers were performed on days 1 to 3, even though evidence suggested that embryos dispelled into the uterus from fallopian tubes were at a post-compaction stage. This meant that initially all embryo transfers were asynchronous transfers. This strategy was imposed upon IVF by the vitro culture conditions of the time, which were sub-optimal for normal rates of blastocyst development. Transferred asynchronously cleavage stage embryos have to adapt to "alien" non- physio-metabolic conditions that may result in embryonic stress and compromised embryo development. In fresh embryo transfer this is further exacerbated by the supraphysiological hormone effects of controlled ovarian stimulation. In addition, there are mechanical factors (i.e. uterine contractility) and time factors, related to the endometrium (i.e., window of implantation) and embryo (i.e., time to hatching), that may reduce the chances of implantation. In contrast, to most other mammalian species the transfer of cleavage stage embryos to human uteruses led to acceptable levels of pregnancy and live birth.

The regulation of synchrony between embryo and endometrium has not been fully addressed clinically in the human. This limitation affects IVF significantly in that up to 30% of embryo transfers may be affected by endometrial receptivity factors. The endometrium is a highly specialized, hormonally regulated tissue which is only receptive to embryo communication/interaction for a self-limiting period referred to as the window of implantation. Currently, there is no way to non-invasively determine the time of optimal receptivity, with IVF transfers performed on the assumption that the WOI was sufficiently wide enough to accommodate implantation in most patients and most treatments. During this period, the endometrial epithelium acquires optimal receptivity by progressing through specific structural, functional, and morphological changes induced by pre-ovulatory estrogen and progesterone and post-ovulatory progesterone, LH, and hCG.

During the last three decades, there has been a major increase in the understanding of embryo physiology and correspondingly major improvements in the in vitro culture technologies used, in particular culture media and incubator technologies. These improvements have resulted in the culture of more good quality cleavage stage embryos and consequently blastocysts after extended culture, increasing embryo utility and the pregnancy capacity of an cycle. The increased implantation rates obtained with blastocyst transfers may be as much to do with embryo quality and stage, i.e., blastocysts have the required bi-directional communication competency needed for implantation, as with the WOI, i.e., the time of blastocyst formation and transfer coincides with the WOI of endometria. Moreover, the presently improved culture conditions may also be changing traditional embryo developmental milestones, in particular, the time to blastulation may be decreasing. An increasing number of blastocysts are being formed on day 4 of culture - ±100 hours post-insemination. Traditionally, day 4 embryos were only assessed for evidence of compaction, which is the developmental stage leading to blastulation and cell differentiation.

Zygotes or embryos that reach developmental milestones first (i.e., syngamy, early cleavage, early compaction and early blastulation) are generally believed to have increased chances of normal developmental potential. In recent artificial frozen embryo transfers (FET) in which blastocysts vitrified on day 4 of culture and transferred on P+4, with blastocysts traditionally transferred on P+5, a high rate of implantation has been observed. In addition, a greater number of these implantations resulted in clinical pregnancies (i.e., a conceptus with normal fetal heart activity). In this prospective randomised control study, the investigators will investigate whether this increased viability, is due either to embryo quality, endometrial receptivity, or a combination of the two factors by randomizing the transfer of day 5 blastocysts to P+4 or P+5.

Conditions

Progesterone Induced Endometrial Receptivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: SINGLE

Study Groups

Progesterone + 4

the transfer of day 5 blastocyst on the 5th day of progesterone supplementation

Group Type: EXPERIMENTAL

Progesterone supplementation

Intervention Type: PROCEDURE

artificial frozen embryo transfers

Progesterone + 5

the transfer of day 5 blastocysts on the 6th day of progesterone supplementation

Group Type: ACTIVE_COMPARATOR

Progesterone supplementation

Intervention Type: PROCEDURE

artificial frozen embryo transfers

Interventions

Progesterone supplementation

artificial frozen embryo transfers

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• a freeze-all cycle

Exclusion Criteria

• patients who do not consent
• patients who retract their consent
• patients with day 4 blastocysts frozen
• patients with no blastocysts frozen

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Antalya IVF

OTHER

Sponsor Role: lead

Responsible Party

Kevin Coetzee

Scientific advisor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Antalya IVF

Antalya, Antalya, Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

Fauser BC, Devroey P. Reproductive biology and IVF: ovarian stimulation and luteal phase consequences. Trends Endocrinol Metab. 2003 Jul;14(5):236-42. doi: 10.1016/s1043-2760(03)00075-4.

Reference Type: BACKGROUND

PMID: 12826330 (View on PubMed)

van de Vijver A, Polyzos NP, Van Landuyt L, Mackens S, Stoop D, Camus M, De Vos M, Tournaye H, Blockeel C. What is the optimal duration of progesterone administration before transferring a vitrified-warmed cleavage stage embryo? A randomized controlled trial. Hum Reprod. 2016 May;31(5):1097-104. doi: 10.1093/humrep/dew045. Epub 2016 Mar 22.

Reference Type: BACKGROUND

PMID: 27005893 (View on PubMed)

Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011 Jun;26(6):1270-83. doi: 10.1093/humrep/der037. Epub 2011 Apr 18.

Reference Type: BACKGROUND

PMID: 21502182 (View on PubMed)

Other Identifiers

AntalyaIVF

Identifier Type: -

Identifier Source: org_study_id