Corpus Luteum in transplanted ovarian tissue:

Author: Claus Yding Andersen

Introduction

A properly functioning corpus luteum (CL) is crucial for establishing a successful pregnancy. One of the main functions of the CL is to secrete (P4), which influences the endometrium, inducing its transformation from a proliferative to a secretory state, thus facilitating embryo implantation. In addition to P4, the CL produces other hormones that act on reproductive organs, promoting conditions favourable for implantation. The CL is the most active endocrine organ in the body, producing up to 40 mg of P4 per day at its peak. It is highly vascularized and often experiences haemorrhagic events, which the ovarian environment can accommodate.

During normal ovarian function, the veins draining the ovary contain high levels of P4, particularly when the CL is active. These veins run in close proximity to the arteries leading to the uterus, allowing for the diffusion of P4 from the ovarian veins into the uterine arteries, ensuring adequate P4 exposure to the uterus.

In the context of ovarian tissue transplantation for fertility preservation, the cortex is often positioned into the remaining ovary (whether it is menopausal or not), which likely supports the development of a normal CL. However, when ovarian tissue is transplanted outside the ovary, such as into a peritoneal pocket, the conditions for CL development are substantially altered. The ovarian environment, including its vascular structure, is absent, and the veins draining the transplant no longer influence the uterine arteries, which is likely to affect P4 delivery to the endometrium.

Scientific Question

The primary question addressed by this proposal is: How does ovarian tissue transplantation outside the ovary affect the function of the CL in terms of hormonal secretion and durability?

More specifically, the aim is to determine whether CLs developing in transplanted tissue outside the ovary maintain similar P4 and hormone concentrations to those of a CL formed within the remaining ovary after transplantation or a normal CL.

Preliminary results from previous ovarian tissue transplantations in Denmark, not reported in the scientific literature, suggest that CLs formed in tissue transplanted outside the ovary produce lower P4 levels compared to those developing within the ovary and may affect pregnancy outcome.

If this is confirmed, such data would have clinical implications, as it would suggest that luteal phase support may be necessary for women who undergo ovarian tissue transplantation with tissue positioned outside the ovary in order to achieve pregnancy, both in natural menstrual cycles and during assisted reproductive technology (ART) procedures.

Furthermore, results of such a study will have clinical implications beyond fertility preservation and transplantation of ovarian tissue. If the circulatory concentrations of P4 are independent of whether the tissue is transplanted to the remaining ovary or somewhere outside of the ovary and pregnancy rates remain similar between the two transplantation sites this suggests that luteal phase support as commonly used in ART does not need to be applied near the uterus as in the vagina for instance but may be administered in for instance circulation because the uterine “first path effect” will be eliminated in those patients having tissue positioned outside of the ovary.

Study Design

This study will involve a retrospective analysis of P4 and other hormone concentrations following ovarian tissue transplantation, with a focus on the transplantation site and achievement of pregnancy and pregnancy outcome. Women will be monitored with frequent blood sampling, with cycle days carefully recorded to ensure accurate hormone measurements.

Additionally, the study may explore the effect of transplant site on CL function within individual women, as ovarian tissue is often transplanted at multiple sites to ensure an adequate number of cortex pieces. For instance, tissue may be transplanted both into the ovary and into a peritoneal pocket and ovulation will alternate between transplantation sites.

 

Invitation to Contribute

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