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

Ovarian tissue cryopreservation (OTC) is mainly used for fertility preservation in girls and women facing a gonadotoxic treatment. If the woman subsequently becomes menopausal, the ovarian tissue may be transplanted to regain ovarian function, including fertility. The method was developed more than two decades ago and today thousands of women worldwide have undergone OTC. Fewer than 500 patients have had tissue transplanted and close to 100% of those regain ovarian function. Several technical aspects of OTC are now becoming more established, including high quantitative follicle survival, defining the size of the tissue resulting in optimal tissue revascularisation and follicle loss resulting from transport of ovarian tissue prior to freezing. We have used OTC to safeguard fertility in patients with genetic diseases, which for some diagnoses is purely experimental, as no transplantations is yet been performed. Usage of OTC beyond fertility is now also being considered; here, the endocrine function of follicles is the focus. It has been suggested that ovarian tissue stored in the reproductive years may be used to avoid premature ovarian insufficiency (POI) when there is a familial disposition or to postpone menopause in patients with an increased risk of osteoporosis or cardiovascular diseases. The benefit of OTC beyond fertility requires, however, actual clinical studies. The current review includes several recent technical aspects with contributions from Denmark building on some of the early work by Roger Gosden.

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Premature Ovarian Insufficiency: Procreative Management and Preventive Strategies

Biomedicines ◽

10.3390/biomedicines7010002 ◽

2018 ◽

Vol 7 (1) ◽

pp. 2 ◽

Cited By ~ 6

Author(s):

Jennifer Chae-Kim ◽

Larisa Gavrilova-Jordan

Keyword(s):

Quality Of Life ◽

At Risk ◽

Fertility Preservation ◽

Reproductive Function ◽

Premature Ovarian Insufficiency ◽

Preventive Strategies ◽

Ovarian Insufficiency ◽

Reproductive Aged Women

Premature ovarian insufficiency (POI) is the loss of normal hormonal and reproductive function of ovaries in women before age 40 as the result of premature depletion of oocytes. The incidence of POI increases with age in reproductive-aged women, and it is highest in women by the age of 40 years. Reproductive function and the ability to have children is a defining factor in quality of life for many women. There are several methods of fertility preservation available to women with POI. Procreative management and preventive strategies for women with or at risk for POI are reviewed.

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Fertility Preservation: Current and Future Perspectives for Oncologic Patients at Risk for Iatrogenic Premature Ovarian Insufficiency

BioMed Research International ◽

10.1155/2018/6465903 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Sara Pinelli ◽

Stefano Basile

Keyword(s):

Fertility Preservation ◽

Ovarian Tissue ◽

Premature Ovarian Insufficiency ◽

Ovarian Tissue Cryopreservation ◽

Adult Women ◽

Childbearing Age ◽

Ovarian Insufficiency ◽

Require Time ◽

Early Diagnosis Of Cancer ◽

Oncologic Patients

Progress in recent years in the efficacy of oncologic treatment and early diagnosis of cancer has determined an increase in life expectance in cancer patients. About 10% of all cancer cases affect women younger than 45 years; therefore nowadays approximately 5-6% of the population in childbearing age consists in cancer survivors. A crucial issue is the high risk of premature ovarian insufficiency due to possible gonadotoxic effects of oncologic treatments. Considering combined chemotherapy, radiation therapy, and bone marrow transplantation, this risk can reach 92-100%, depending on the age and ovarian reserve of the patient, as well as the schedule and type of therapy. International guidelines recommend addressing all the patients diagnosed with a neoplasia treatable with potentially gonadotoxic therapies to fertility preservation. Moreover, fertility preservation also seems to reserve fascinating implications for women who want to delay childbearing for social reasons or women affected with endometriosis, who could receive unexpected opportunities. At present, the most widespread techniques to preserve fertility in adult women are embryo or oocyte cryopreservation, depending on the presence of a partner or according to legislative issues, but these procedures require time for ovarian stimulation. In prepubertal patients or when there is no possibility of delaying chemotherapy, ovarian tissue cryopreservation and subsequent transplantation represent the main strategy.

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Fertility preservation in premature ovarian insufficiency secondary to FSH receptor gene mutation: is there a new hope?

Fertility and Sterility ◽

10.1016/j.fertnstert.2013.07.1271 ◽

2013 ◽

Vol 100 (3) ◽

pp. S234

Author(s):

P. Lehmann ◽

R. Antaki ◽

C. Sylvestre ◽

S. Phillips ◽

F. Bissonnette ◽

...

Keyword(s):

Fertility Preservation ◽

Gene Mutation ◽

Receptor Gene ◽

Premature Ovarian Insufficiency ◽

Fsh Receptor ◽

Ovarian Insufficiency ◽

Fsh Receptor Gene

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Fertility Preservation for Women with Sickle Cell Disease (SCD)

Blood ◽

10.1182/blood.v126.23.3408.3408 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3408-3408 ◽

Cited By ~ 1

Author(s):

Torie C Plowden ◽

Nicole M Millan ◽

Carter M Owen ◽

Mae W Healy ◽

Nicole K Banks ◽

...

Keyword(s):

Fertility Preservation ◽

Conflicts Of Interest ◽

Poor Response ◽

Oocyte Retrieval ◽

Controlled Ovarian Hyperstimulation ◽

Underlying Disease ◽

Premature Ovarian Insufficiency ◽

Cell Transplant ◽

Ovarian Insufficiency ◽

Future Fertility

Abstract Objective: Peripheral blood stem cell transplant (PBSCT) can now cure SCD in adults, but may result in a loss of future fertility. Little is documented regarding fertility preservation in women with SCD. The aim of this study was to perform fertility preservation for women with SCD scheduled for PBSCT. Design: Prospective cohort of women with SCD undergoing fertility preservation prior to PBSCT at a large research hospital. Materials and Methods: Patients underwent standard controlled ovarian hyperstimulation (COH) using an antagonist protocol cycle with leuprolide trigger under close multidisciplinary (including reproductive endocrinologists and hematologists) monitoring. All patients were continued on therapeutic or started on prophylactic anticoagulation prior to beginning COH, and maintained on hydroxyurea. Results: Nine reproductive aged women were screened; 1 declined participation, 1 was diagnosed with unrecognized premature ovarian insufficiency, 1 had her fertility preservation cycle canceled due to poor response to fertility medications and 2 patients are scheduled for upcoming cycles. The remaining four women (ages 20, 34, 24, 27) successfully underwent COH, transvaginal oocyte retrieval and cryopreservation of mature eggs (n= 8, 13, 15, 21 oocytes, respectively). The third patient underwent two cycles due to low mature oocyte yield from her initial cycle. Headaches were reported by patients 1 and 2 following gonadotropin injections, with a negative neurologic workup including MRI in patient 2. Patient 3 underwent an exchange transfusion on day 10 of stimulation, which did not adversely impact serum reproductive hormone levels. Patients 3 and 4 reported an acute exacerbation of their chronic pain during COH, which responded well to intravenous fluids, IV and oral pain medications. Therefore, despite severe SCD and co-morbid conditions, the side effects were manageable. There were no venous thrombotic events. Conclusion: These results provide support that fertility preservation can be safely performed in women with SCD under the care of a multidisciplinary team. The safest stimulation protocol (i.e. antagonist cycle with leuprolide trigger for final oocyte maturation) was successful in all patients despite multiple risk factors for failed leuprolide trigger. Fertility preservation is important not only before PBSCT to cure their underlying disease, but also because of high rates of premature ovarian insufficiency in the SCD population post-transplant. Support: Intramural NICHD and NHLBI, NIH. Disclosures No relevant conflicts of interest to declare.

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How polymorphic markers contribute to genetic diseases in different populations? The study of inhibin A for premature ovarian insufficiency

Einstein (São Paulo) ◽

10.1590/s1679-45082017ao4052 ◽

2017 ◽

Vol 15 (3) ◽

pp. 269-272 ◽

Cited By ~ 2

Author(s):

Denise Maria Christofolini ◽

Emerson Barchi Cordts ◽

Fernando Santos-Pinheiro ◽

Erika Azuma Kayaki ◽

Mayla Cristina Fernandes Dornas ◽

...

Keyword(s):

Genetic Diseases ◽

Premature Ovarian Insufficiency ◽

Polymorphic Markers ◽

Ovarian Insufficiency ◽

Exon 2 ◽

Pcr Rflp ◽

Different Populations ◽

Study Participants ◽

And Control ◽

Edta Tube

ABSTRACT Objective To verify the incidence of the G679A mutation in exon 2 of the gene inhibin alpha (INHA), in women with secondary amenorrhea and diagnosis of premature ovarian insufficiency, and in controls. Methods A 5mL sample of peripheral blood was collected from all study participants in an EDTA tube and was used for DNA extraction. For the patient group, 5mL of blood were also collected in a tube containing heparin for karyotype, and 5mL were collected in a dry tube for follicle stimulant hormone dosage. All patient and control samples were initially submitted to analysis of the G679A variant in exon 2 of the INHA gene by PCR-RFLP technique. Samples from patients with premature ovarian insufficiency after PCR-RFLP were submitted to Sanger sequencing of the encoding exons 2 and 3. Sequencing was performed on ABI 3500 GeneticAnalyzer equipment and the results were evaluated by SeqA and Variant Reporter software. Results Samples of 70 women with premature ovarian insufficiency and 97 fertile controls were evaluated. The G769A variant was found in only one patient in the Premature Ovarian Insufficiency Group and in no control, and it appears to be rare in Brazilian patients with premature ovarian insufficiency. This polymorphism was previously associated to premature ovarian insufficiency in several populations worldwide. Conclusion There is genetic heterogeneity regarding the INHA gene in different populations, and among the causes of premature ovarian insufficiency.

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Fertility Preservation in Premature Ovarian Insufficiency (POI) Secondary to FSH Receptor Gene (FSHR) Mutation: Is There a New Hope?

Case Reports in Clinical Medicine ◽

10.4236/crcm.2017.610030 ◽

2017 ◽

Vol 06 (10) ◽

pp. 274-280

Author(s):

Pierre-Antoine Pradervand ◽

Roland Antaki ◽

Simon Phillips ◽

C. Sylvestre ◽

Zaki El Haffaf ◽

...

Keyword(s):

Fertility Preservation ◽

Receptor Gene ◽

Premature Ovarian Insufficiency ◽

Fsh Receptor ◽

Ovarian Insufficiency ◽

Fsh Receptor Gene

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Ovarian transposition

memo - Magazine of European Medical Oncology ◽

10.1007/s12254-020-00646-5 ◽

2020 ◽

Vol 13 (4) ◽

pp. 413-415 ◽

Cited By ~ 1

Author(s):

Elisabeth Reiser ◽

Bettina Böttcher ◽

Danijela Minasch ◽

Julian Mangesius ◽

Bettina Toth

Keyword(s):

Fertility Preservation ◽

Radiation Field ◽

Ovarian Function ◽

Ovarian Failure ◽

Cytotoxic Chemotherapy ◽

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency ◽

Ovarian Transposition

SummaryCytotoxic chemotherapy regimens and radiotherapy can lead to acute ovarian failure, premature ovarian insufficiency and menopause. Fertility preservation options before radiotherapy include ovarian transposition, where one or both ovaries are placed outside the radiation field. However, the efficacy of ovarian transposition is questioned, as the conservation of ovarian function varies between 17 and 95% in the literature.

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