Fertility preservation for genetic diseases leading to premature ovarian insufficiency (POI)

Abstract

Purpose The current review aims to summarize the data available concerning the applicability of fertility preservation techniques to genetic conditions at risk of premature ovarian insufficiency (POI). Methods A literature review through the PubMed Database was carried out. Results About 10% of cases of POI is related to genetic diseases. The most frequent conditions associated with POI are Turner syndrome and fragile X pre-mutation; mutation of BRCA 1-2 genes and several other mutations and genetic syndromes have recently been highlighted, although they rarely occur. If a diagnosis is issued before POI onset, counseling on currently available fertility preservation techniques is advisable. In case of spontaneous menarche (this can occur variably depending on the mutation) established techniques like embryo or oocyte cryopreservation can be proposed, even if, in some cases, their effectiveness may be reduced by ovarian alterations connected to the mutation. Ovarian tissue cryopreservation has recently been defined as an established medical procedure for fertility preservation in young cancer patients and may be an option for prepubertal patients. However, it is still experimental in special populations with genetic diseases causing POI. New innovative experimental techniques, like in vitro maturation of immature oocytes (IVM) and vitro activation (IVA) of immature follicles on ovarian tissue, have shown limited but encouraging data and they will be probably available in the near future. For a correct riskbenefit evaluation, the following aspects should be considered: actual knowledge about the pathology-specific efficacy of the various techniques, the average age of onset of POI, the possible risks associated with the procedure in relation to the underlying pathology, the probability of spontaneous conception, as well as the health implications of a possible future pregnancy.. Conclusions Fertility preservation techniques represent a crucial opportunity for patients with genetic risk of POI. Early diagnosis increases the chances to apply these techniques. No specific recommendations concerning fertility preservation for each genetic pathology are available, and clinicians should first counsel the patient and her relatives about known risks and benefits of the available techniques, both those established and those considered as experimental.

The Trends and Hotspots in Premature Ovarian Insufficiency Therapy from 2000 to 2022

“…Ovarian tissue cryopreservation may be an option to preserve fertility in prepubertal girls and young women who require immediate chemotherapy. It has some advantages, especially for prepubertal patients: no need for ovarian stimulation, thus, no further risk for estrogen-sensitive cancer types, and preservation of more and better-quality primordial follicles of the ovarian cortex [ 38 , 39 ]. After 2018, there was a shift from hormone replacement therapy to more innovative treatment strategies.…”

Identification and Validation of Autophagy-Related Genes in Primary Ovarian Insufficiency by Gene Expression Profile and Bioinformatic Analysis

“…For patients with genetic risk of POI, novel methods aiming at fertility preservation can benefit them a lot through early diagnosis. Recent research, for instance, revealed that there was close correlation between POI and the mutations of BRCA [ 46 ]. BRCA can bind to various essential regulatory proteins and regulate gene expression [ 47 ], which make it possible for BRCA to play a novel role in the regulation of autophagy [ 48 ].…”

Experimental Evidence of 2,3,7,8-Tetrachlordibenzo-p-Dioxin (TCDD) Transgenerational Effects on Reproductive Health

“…There is unquestionable evidence that puberty disorders and menstrual cycle abnormalities, endometriosis, PCOS, subfertility, and POI as well as adverse pregnancy outcomes are multifactorial, with a strong genetic predisposition modulated by the actual ED exposure [80][81][82][83]. However, experimental studies on TCDD effects clearly suggest that ancestral ED exposure through transgenerational epigenetic inheritance may also play a significant role in the pathophysiology of all female reproductive disorders, and this needs to be considered.…”