P-462 Reproductive outcomes in a cohort of Danish women following auto-transplantation of frozen/thawed ovarian tissue from a single center
Authors: Colmorn L.B , Tønnes Pedersen A , Larsen E.C , Kristensen S.G , Rosendahl M , Yding Andersen C , Tryde Macklon K.L 
Published: June 2022

Abstract

Study question
What is the reproductive outcome from ovarian tissue transplantation (OTT) from a single, experienced center.

Summary answer
The overall delivery rate was 41% (16/39) per woman and a total of 20 children to 39 women is expected.

What is known already
Ovarian tissue cryopreservation (OTC) is a well-established procedure for fertility preservation in girls and young women prior to gonadotoxic treatment and has shown to be a safe and promising method to restore fertility, with more than 200 healthy children born worldwide. Initial recovery of endocrine function is very high, although the longevity of the grafted tissue varies. The success of OTT is multifactorial, and important factors such as high age and poor ovarian reserve at OTC, as well as pelvic radiation are known to impair the chances of success.

Study design, size, duration
This is a single center, combined retro- and prospective cohort study including 40 women undergoing a total of 53 OTTs from the Fertility Clinic at Rigshospitalet University Hospital of Copenhagen, Denmark between 2003 and 2021.

Participants/materials, setting, methods
All women, who underwent OTT, were included in the study. End of follow up was December 31st, 2021. Information about diagnoses, gonadotoxic treatment, gynecologic (incl. endocrine parameters) and obstetric history was retrieved from medical records. Permission to obtain retrospective data from 1999 to 2020 was given by the Danish Patient Safety Authorities (jrn 3-3013-2790/1) and prospective data-collection was given by informed consent from the patients from 2020 and onwards.

Main results and the role of chance
Mean age at OTC was 28.5+5.5 years. Indications for OTC were malignant (n = 34) or benign diseases (n = 6). Mean time to first OTT was 4.2 years and mean age 33.0+5.4 years. At OTT, 19 women had POI (FSH&gt;25 IU/L and amenorrhea), 10 were perimenopausal (intermittent FSH &gt;25 IU/L) and 11 were low responders (AMH&lt;5pmol/L), with normal endocrine parameters but signs of infertility. Minimal follow up was 11 months and maximum 17 years from OTT.
From 39 women with a pregnancy wish, 11 (28%) gave birth to a total of 15 children. In addition, 5 pregnancies are currently ongoing in the last trimester. The overall delivery rate was 51% (20/39) (including 5 ongoing) and 41% (16/39) per woman. Of 20 deliveries, 60% were conceived naturally and 40% from ART. Nineteen children were delivered following the first OTT. Four women had 2 children, of whom one had her second child following the second OTT.
Initial activation of the grafted tissue, defined by a drop of FSH to &lt; 25 IU/L within 6 months, was seen in 18/19 (95%) women with POI prior to OTT. One woman experienced total graft failure.
Data on endocrine function of the grafted tissue will be presented at the meeting.

Limitations, reasons for caution
This study is based on information from medical records in public Danish hospitals, where information of all deliveries in Denmark is available. Pregnancies and deliveries outside Denmark might therefore not be included, why the total number could be slightly underestimated.

Wider implications of the findings
OTC with OTT is an efficient and encouraging way to restore fertility in a selected group of young women with a high risk of infertility following gonadotoxic treatment. Further, our data, from a specialized and experienced center, shows a good chance of livebirth and initial recovery of endocrine function.

Trial registration number
3-3013-2790/1