Administration of Human Chorionic Gonadotrophin Before Secretory Transformation of Frozen-thawed Embryo Transfer Cycles
Status:
Recruiting
Trial end date:
2022-05-01
Target enrollment:
Participant gender:
Summary
To investigate the role of parenteral hCG used for the transfer of cryopreserved- thawed
embryos with HRT cycles in the outcome of artificially prepared FET cycles. Frozen-thawed
embryo transfer (FET) cycles has increased recently contributing to about 30% of ART
cycles,which improved pregnancy outcome from each oocyte retrieval.
Despite the extensive research in all areas of reproductive medicine and breakthroughs in ART
to improve cycle outcome, the efficacy of embryo implantation is relatively low and continues
to be the rate limiting factor. Successful embryo implantation is complicated process that
requires synchrony between good-quality embryos and receptive endometrium. It is associated
with the liberation and presence of various mediators secreted from both the developing
embryo and the endometrium such as cyclic adenosine monophosphate (cAMP), relaxin,
gonadotropin, prostaglandin E2 (PGE2), and glycoprotein. The achievement of optimal
endometrial preparation in FET cycles is important not only for proper implantation but also
for pregnancy outcome. However, no consensus on the optimal endometrial preparation protocol
and various protocols are used in FET: modified natural, stimulated and artificial cycles,
with the latter is the most commonly used. In artificial cycle, the endometrium is prepared
by administration of exogenous oestrogen followed by progesterone to induce secretory
transformation before embryo transfer (ET). Both hormones are essential for adequate
endometrial preparation for implantation. Another key molecule that principally controls
implantation is the human chorionic gonadotropin (hCG),which is one of the initial embryonic
signals and the major embryoendometrial relationship regulator. It is expressed by blastocyst
before the implantation, then increasingly produced the syncytiotrophoblast after
implantation. The LH and hCG receptors are present in the human endometrium, via these
receptors, local hCG has several paracrine effects at implantation site that modulate
endometrial receptivity and finally lead to a stable implantation. It has been found to
prolong the window of receptivity and enhance endometrial
angiogenesis through down regulation of insulin- like growth factor- binding protein 1
(IGFBP-1) and increasing vascular endothelial growth factor (VEGF), respectively. It also
interferes with the biosynthesis of leukemia inhibitory factor and macrophage colony
stimulating factor (LIF and M-CSF) both are involved in the embryo-maternal cross-talk and
modulate trophoblast differentiation. In addition, hCG has been shown to have autocrine
effects on the trophoblasts themselves, leading to increased differentiation and invasive
potential, "hCG could well be a key regulator, triggering whether or not the embryo will
implant". Although several studies investigated the role of intrauterine administration of
hCG before embryo transfer on IVF outcome, this approach is not recommended yet and many
reports are conflicting. On the other hand, because parenteral hCG is not usually used for
the transfer of cryopreserved- thawed embryos with HRT cycles as ovulation is usually
suppressed, there are few data about the benefit of hCG administration in the outcome of
artificially prepared FET cycles.