Loss of ESRP1 blocks mouse oocyte development and leads to female infertility.

Alternative splicing (AS) contributes to gene diversification, but the AS program during germline development remains largely undefined. Here, we interrupted pre-mRNA splicing events controlled by epithelial splicing regulatory protein 1 (ESRP1) and found that it induced female infertility in mice. Esrp1 deletion perturbed spindle organization, chromosome alignment and metaphase-to-anaphase transformation in oocytes. The first polar body extrusion was blocked during oocyte meiosis owing to abnormal activation of spindle assembly checkpoint and insufficiency of anaphase-promoting complex/cyclosome in Esrp1-knockout oocytes. Esrp1-knockout hampered follicular development and ovulation; eventually, premature ovarian failure occurred in six-month-old Esrp1-knockout mouse. Using single-cell RNA-seq analysis, 528 aberrant AS events of maternal mRNA transcripts were revealed and were preferentially associated with microtubule cytoskeletal organization. Notably, we found that loss of ESRP1 disturbed a comprehensive set of gene-splicing sites - including those within Trb53bp1, Rac1, Bora, Kif2c, Kif23, Ndel1, Kif3a, Cenpa and Lsm14b - that potentially caused abnormal spindle organization. Collectively, our findings provide the first report elucidating the ESRP1-mediated AS program of maternal mRNA transcripts, which may contribute to oocyte meiosis and female fertility in mice.

Genitourinary symptoms and sexual function in women with primary ovarian insufficiency.

OBJECTIVE: There are limited studies on urogenital symptoms in women who experience menopause before the age of 40 years due to primary ovarian insufficiency (POI) or bilateral oophorectomy (surgical POI). This study aimed to compare the urogenital symptoms, including sexuality, of women with POI to those without the condition. METHODS: This cross-sectional study conducted was in seven Latin American countries, in which postmenopausal women (with POI and non-POI) were surveyed with a general questionnaire, the Menopause Rating Scale (MRS) and the six-item Female Sexual Function Index (FSFI-6). The association of premature menopause with more urogenital symptoms and lower sexual function was evaluated with logistic regression analysis. RESULTS: Women with POI experience more urogenital symptoms (MRS urogenital score: 3.54 ± 3.16 vs. 3.15 ± 2.89, p < 0.05) and have lower sexual function (total FSFI-6 score: 13.71 ± 7.55 vs. 14.77 ± 7.57 p < 0.05) than women who experience menopause at a normal age range. There were no significant differences in symptoms when comparing women based on the type of POI (idiopathic or surgical). After adjusting for covariates, our logistic regression model determined that POI is associated with more urogenital symptoms (odds ratio [OR]: 1.38, 95% confidence interval [CI] 1.06-1.80) and lower sexual function (OR: 1.67, 95% CI 1.25-2.25). CONCLUSION: POI, whether idiopathic or secondary to bilateral oophorectomy, is associated with symptoms that affect vaginal and sexual health.

Reproductive health in Turner syndrome: A narrative review.

Turner syndrome (TS), a common chromosomal abnormality affecting females, is associated with partial or complete loss of the second sex chromosome. Although the classic karyotype is 45, X, the detection of mosaic TS is increasing. TS is a multi-system disorder with significant endocrine, cardiovascular and reproductive impacts. Accelerated ovarian follicular loss leads to primary amenorrhoea or premature ovarian insufficiency and infertility. Early diagnosis and counselling regarding hormone replacement therapy and future reproductive capacity, including fertility preservation, are essential to improve reproductive outcomes. Pubertal induction or estrogen replacement is usually required to optimise long-term health outcomes; however, initiation may be delayed due to delayed diagnosis. Spontaneous pregnancy occurs in a small number of women; however, many require donor oocytes and assisted reproductive technology to achieve a pregnancy. Pregnancy is a high risk especially when associated with congenital heart disease. Prepregnancy counselling by the multidisciplinary team (MDT) to identify contraindications and optimise pre-existing health issues is essential. Pregnancy management should be led by a maternal-fetal medicine unit with input from the MDT. This review examines reproductive health outcomes in women with TS and how best to manage them to reduce health risks and improve maternal and neonatal outcomes.

The risk of depressive and anxiety symptoms in women with premature ovarian insufficiency: a systematic review and meta-analysis.

Premature ovarian insufficiency (POI) appears to be associated with depressive and anxiety symptoms. However, there is a lack of high-quality evidence relating to the risk of patients with POI developing depression or anxiety. Therefore, we conducted a systematic review and meta-analysis to quantify the risk of depressive and anxiety symptoms in women with POI. We searched English and Chinese databases to evaluate the risk of depression and anxiety disorders in patients with POI. The final search date was November 2021. The risk was quantified using meta-analysis, with an estimation of pooled odds ratio (OR) and 95% confidence interval (CI). Sources of heterogeneity were explored by subgroup analysis. A total of seven primary studies with 1316 individuals were included, five of which were related to depression and six to anxiety disorders. All included articles were case-control studies of high quality. Patients with POI were associated with a higher odds of depression and anxiety (depression: OR = 3.33, 95% CI = 2.31-4.81, P < 0.001; anxiety: OR = 4.89, 95% CI = 3.28-7.30, P < 0.001). Subgroup analysis also indicated that patients with POI are at a higher risk of anxiety and depression. POI appears to be associated with a high risk of depression and anxiety. Early psychosocial assessment and regular screening of patients with POI are also necessary. In addition, it is important to consider the mental health of patients with POI.

Specifics of infertility treatment in women with premature ovarian failure.

Premature ovarian failure (POF, POI - premature ovarian insufficiency) is a serious situation for a woman with reproductive plans that more or less precludes having her own bio-logical child. In addition to the lack of functional oocytes in the ovaries, it is also a premature lack of sex hormones, which has an overall negative effect on health. The article guides us through care both in the clinic of the gynecologist and through treatment in the center of reproductive medicine. The dia-gnosis and treatment of POF illustrates some endocrinological principles and connections.

Two consecutive pregnancies in a patient with premature ovarian insufficiency in the course of classic galactosemia and a review of the literature.

AIM: To present a case report of a patient with classic galactosemia and the Q188R/K285N GALT mutation, who conceived spontaneously twice despite severe ovarian failure. A review of the literature is included. MATERIALS AND METHODS: A 20-year-old patient with classic galactosemia and premature ovarian insufficiency (POI) came to our attention. We performed a routine hormonal and ultrasound examination confirming low ovarian reserve. Due to low rates of pregnancies in individuals with POI (5%-10%), we were almost certain of the infeasibility of pregnancy. RESULTS: Surprisingly, several months after hospitalization, the patient conceived without any medical intervention and less than a year after the first birth she became pregnant again. While reviewing the literature, 90 pregnancies among galactosemic patients were identified. CONCLUSIONS: Ovarian failure is a long-term diet-independent complication of classic galactosemia, pertaining to about 90% of affected individuals. This case confirms its unpredicted course, as even the presence of unfavorable factors (absence of spontaneous puberty, early diagnosis of POI, undetectable AMH) may not preclude the chance for conception.

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

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 risk-benefit 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.

Low-Intensity Extracorporeal Shock Wave Therapy Promotes Bladder Regeneration and Improves Overactive Bladder Induced by Ovarian Hormone Deficiency from Rat Animal Model to Human Clinical Trial.

Postmenopausal women with ovary hormone deficiency (OHD) are subject to overactive bladder (OAB) symptoms. The present study attempted to elucidate whether low-intensity extracorporeal shock wave therapy (LiESWT) alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity to influence bladder function in OHD-induced OAB in human clinical trial and rat model. The ovariectomized (OVX) for 12 months Sprague-Dawley rat model mimicking the physiological condition of menopause was utilized to induce OAB and assess the potential therapeutic mechanism of LiESWT (0.12 mJ/mm2, 300 pulses, and 3 pulses/second). The randomized, single-blinded clinical trial was enrolled 58 participants to investigate the therapeutic efficacy of LiESWT (0.25 mJ/mm2, 3000 pulses, 3 pulses/second) on postmenopausal women with OAB. The results revealed that 8 weeks' LiESWT inhibited interstitial fibrosis, promoted cell proliferation, enhanced angiogenesis protein expression, and elevated the protein phosphorylation of ErK1/2, P38, and Akt, leading to decreased urinary frequency, nocturia, urgency, urgency incontinence, and post-voided residual urine volume, but increased voided urine volume and the maximal flow rate of postmenopausal participants. In conclusion, LiESWT attenuated inflammatory responses, increased angiogenesis, and promoted proliferation and differentiation, thereby improved OAB symptoms, thereafter promoting social activity and the quality of life of postmenopausal participants.

Endothelial cell-specific-molecule-1 (endocan) levels in women with premature ovarian insufficiency: a prospective comparative study.

There is an increased risk of cardiovascular disease in women with premature ovarian insufficiency (POI). A relationship between cardiovascular disease and endocan levels has been shown. Endocan is a marker that is prominent in many diseases caused by endothelial dysfunction and can be measured in the blood. POI is also associated with endothelial dysfunction. The causes of POI include chromosomal and genetic defects, autoimmune processes, chemotherapy, radiation, infections and surgery, but many are unidentified (idiopathic). This study aimed to evaluate serum endocan levels in women with idiopathic POI. The blood for analysis was obtained at the early follicular phase of the menstrual cycle and endocan levels were measured using a commercially available enzyme-linked immunosorbent assay kit. There were 38 patients with idiopathic POI in the study group and 39 healthy subjects in the control group. The median ages of the women were not significantly different between the groups 34 [7] years vs. 34 [7] years, respectively (p = .862). The median endocan level was not different in the POI and control group 769 [727] vs. 1077 [403] pg/mL, respectively (p = .603). Endocan is not associated with the cardiovascular diseases risk linked with endothelial dysfunction in idiopathic POI. Clinical trial number: NCT03932877 (Clinicaltrials.gov)IMPACT STATEMENTWhat is already known on this subject? There is an increased risk of cardiovascular disease in premature ovarian insufficiency (POI) due to the decreased level of oestrogen, which is linked with endothelial dysfunction.What do the results of this study add? This study showed that endocan is not associated with the cardiovascular disease risk linked with endothelial dysfunction in idiopathic POI.What are the implications of these findings for clinical practice and/or further research? A marker to be used to predict the risk of cardiovascular disease in patients with POI could facilitate in improving the quality of life of these patients. Moreover, advantageous and easy-to-measure markers are needed in larger sample studies to better understand the cardiovascular diseases risk in POI.

Mutation in ALOX12B likely cause of POI and also ichthyosis in a large Iranian pedigree.

Premature ovarian insufficiency (POI) is a clinically and etiologically heterogeneous disorder characterized by menstrual irregularities and elevated levels of FSH before age of 40 years. Genetic anomalies are among the recognized causes of POI. Here, we aimed to identify the genetic cause of POI in an inbred pedigree with nine POI and two ichthyosis-affected members. Inheritance of POI and ichthyosis were, respectively, dominant and recessive. Reproduction-related information and measurements of relevant hormones were obtained. Genetic studies included homozygosity mapping, linkage analysis, exome sequencing, and screening of candidate variants. A mutation within ALOX12B, which is a known ichthyosis causing gene, was identified as cause of ichthyosis. ALOX12B encodes a protein involved in steroidogenesis and lipid metabolism. Considering the importance of steroidogenesis in reproduction functions, the possibility that the ALOX12B mutation is also cause of POI was considered. Screenings showed that the mutation segregated with POI status. Linkage analysis with respect to POI identified a single strongly linked locus (LOD > 3) that includes ALOX12B. Exome sequencing on POI-affected females identified the mutation in ALOX12B and also a sequence variation in SPNS2 within the linked locus. A possible contribution of the SPNS2 variation to POI was not strictly ruled out, but various data presented in the text including reported association of variations in related gene ALOX12 with menopause-age and role of ALOX12B in atretic bovine follicle formation argue in favor of ALOX12B. It is, therefore, concluded that the mutation in ALOX12B is the likely cause of POI in the pedigree.

Serum anti-Müllerian hormone levels are associated with low bone mineral density in premenopausal women.

OBJECTIVE: To investigate the associations between anti-Müllerian hormone (AMH) and bone mineral density (BMD) induced by ovarian insufficiency in premenopausal women. METHODS: Subjects were consecutively enrolled from January 2015 to December 2018. Dual energy X-ray absorptiometry (DXA) examination was set as the gold standard, with T-scores less than -2.5/1 as thresholds for the definition of osteoporosis (OP)/osteopenia. RESULTS: A total of 87 subjects were included in the low BMD group, and 39 subjects were included in the control group. Serum AMH levels were decreased significantly in the low BMD group (p < 0.05) with a negative correlation between AMH and age. Strong positive correlations between AMH and BMD/T-score existed in all subjects and subjects with low BMD, and remained even after age adjustment. An exploratory multivariate regression model indicated that age and AMH remained predictive and might be independent risk factors with adjusted odds ratios (ORs) of 0.9 (p = 0.009) and 36 (p < 0.001), respectively. The receiver operating characteristic (ROC) curve analysis estimated that the sensitivity and specificity were 78.2 and 76.9%, respectively, for identifying low BMD subjects from controls when the cut-off value for AMH was set to 0.800 ng/mL. CONCLUSIONS: Serum AMH levels are associated with low BMD in premenopausal women with suspected ovarian insufficiency.

Premature ovarian failure in patients affected by systemic lupus erythematosus: a cross-sectional study.

OBJECTIVES: We evaluated age at natural menopause and the prevalence of premature ovarian failure (POF) in a monocentric Caucasian cohort of patients with systemic lupus erythematosus (SLE). METHODS: In this cross-sectional study, we enrolled women affected by SLE compared with healthy controls (HC) to investigate data about natural menopause (amenorrhoea for at least 12 months at ≥40 years) and POF (amenorrhoea for at least 12 months at <40 years). RESULTS: We enrolled 196 SLE (median age 47.0 years, IQR 16.7; median disease duration 132 months, IQR 180) and 90 HC (median age 49.9 years, IQR 15.0). Ninety-four SLE (48.0%) and 26 HC (23.4%) were menopausal: median age at onset was significantly lower in SLE than HC (47 years, IQR 8.0 vs. 50.5 years, IQR 4; p=0.0001). POF was registered in 17% of the SLE, and in none of the HC (p<0.0001). POF was significantly associated with anti-Sm (p=0.0004), anti-RNP (p=0.02), anti-cardiolipin (p=0.0008), lupus anticoagulant (p=0.0002), treatment with cyclophosphamide (p=0.0001), azathioprine (p=0.0001), mycophenolate mofetil (p=0.0001), cyclosporine A (p=0.007). CONCLUSIONS: SLE patients develop menopause at a younger age; moreover, a higher POF frequency was observed in SLE patients in comparison with HC. POF is associated with specific SLE-related autoantibodies and the use of immunosuppressant drugs, in particular cyclophosphamide.

Tailored hormonal approach in women with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is probably one of the most devastating diagnoses for women of reproductive age. The major implications for fertility, climacteric symptoms, and quality of life, the great impact of long-term consequences such as bone loss and cardiovascular health, and the lack of a coherent and shared clinical approach make the choice for the right hormonal therapy challenging. In this review we propose an integrated and patient-based hormonal approach for women with POI, from puberty to late reproductive age.

DuoStim: a new option for fertility preservation for a woman with Turner syndrome.

INTRODUCTION: Turner syndrome (TS) is associated with hypergonadotropic hypogonadism due to gonadal dysgenesis, which results in premature ovarian failure and subsequent infertility. Therefore, counseling and evaluation for fertility preservation are required as early as possible for women with TS. CASE PRESENTATION: A 23-year-old unmarried woman with mosaic TS (45, X [4/30] 46, XX [26/30]) presented to the pediatric department of our hospital for fertility counseling; she was accompanied by her mother. She was referred to the reproduction center of our hospital for ovarian reserve assessment and counseling regarding fertility preservation. We decided to retrieve oocytes using DuoStim as the controlled ovarian stimulation protocol. During the first and second oocyte retrievals, a total of 17 (9 and 8, respectively) mature metaphase II oocytes were cryopreserved. CONCLUSION: DuoStim may be a useful option for fertility preservation for women with TS and reduced ovarian reserve. This new strategy may obtain the required number of oocytes in the shortest time and preserve the future fertility of women with TS.

The role of oxidative stress on subclinical atherosclerosis in premature ovarian insufficiency and relationship with carotid intima-media thickness.

Objective: We aimed to investigate the relationship between oxidative stress (OS) and subclinical atherosclerosis in patients with premature ovarian insufficiency (POI), by analyzing the dynamic thiol/disulfide homeostasis (TDH) parameters as an OS marker and carotid intima-media thickness (CIMT).Materials and methods: A total of 69 women, 34 with POI and 35 healthy controls were included in this prospective cross-sectional study. TDH parameters (plasma native thiol, total thiol, disulfide, disulfide/native thiol, native thiol/total thiol, and disulfide/total thiol ratios) and CIMT were measured and compared between the two groups.Results: In primary ovarian insufficiency group, native thiol (p=.009) and total thiol (p=.010) levels were significantly decreased, and CIMT values were significantly increased (p= <.001). CIMT values were negatively correlated with native thiol (r=-0.553, p=.001) and total thiol levels (r=-0.565, p=.001); and positively correlated with age (r = 0.457, p=.007), BMI (r = 0.408, p=.017), and total cholesterol (r = 0.605, p<.001) in POI group.Conclusions: Decreased native thiol and total thiol levels demonstrate the defective anti-oxidant mechanism in POI. Negative correlation between native thiol, total thiol levels, and CIMT means the presence of abnormal anti-oxidant mechanisms may play a role in the development of subclinical atherosclerosis in patients with POI. This is a novel report on the mechanism of subclinical atherosclerosis in women with POI, which needs to be supported with further studies evaluating the pathophysiology of OS.

Impact of BRCA1 and BRCA2 mutations on ovarian reserve and fertility preservation outcomes in young women with breast cancer.

PURPOSE: To determine the impact of BRCA1 and BRCA2 mutations on ovarian reserve and fertility preservation outcome. The main purpose and research question of the study is to determine the impact of BRCA1 and BRCA2 mutations on ovarian reserve and fertility preservation outcomes. METHODS: Prospective study: 67 breast cancer patients between 18 and 40 years old, undergoing a fertility preservation by means of oocyte storage were considered. Inclusions criteria for the study were age between 18 and 40 years old, BMI between 18 and 28, breast cancer neoplasm stage I and II according to American Joint Committee on Cancer classification (2017) and no metastasis. EXCLUSION CRITERIA: age over 40 years old, BMI < 18 and > 28, breast cancer neoplasm stage III and IV and do not performed the BRCA test. A total of 21 patients had not performed the test and were excluded. Patients were divided into four groups: Group A was composed by 11 breast cancer patients with BRCA 1 mutations, Group B was composed by 11 breast cancer patients with BRCA 2 mutations, Group C was composed by 24 women with breast cancer without BRCA mutations, and Group D (control) was composed by 181 normal women. RESULTS: Group A showed significant lower AMH levels compared to Group C and D (1.2 ± 1.1 vs 4.5 ± 4.1 p < 0.05 and 1.2 ± 1.1 vs 3.8 ± 2.5 p < 0.05). BRCA1 mutated patients showed a significant lower rate of mature oocytes (MII) compared to Group C (3.1 ± 2.3 vs 7.2 ± 4.4 p < 0,05) and Group D (3.1 ± 2.3 vs 7.3 ± 3.4; p < 0,05). Breast cancer patients needed a higher dose of gonadotropins compared to controls (Group A 2206 ± 1392 Group B2047.5 ± 829.9 Group C 2106 ± 1336 Group D 1597 ± 709 p < 0,05). No significant differences were found among the groups considering basal FSH levels, duration of stimulation, number of developed follicles, and number of total retrieved oocytes. Regarding BRCA2 mutation, no effect on fertility was shown in this study. CONCLUSIONS: The study showed that BRCA1 patients had a higher risk of premature ovarian insufficiency (POI) confirmed by a diminished ovarian reserve and a lower number of mature oocytes suitable for cryopreservation.

The effect of premature ovarian failure on inner ear function.

The aim of this study was to test whether hearing function is impaired in women with premature ovarian failure. Thirty (30) women with premature ovarian failure (POF), 30 women in menopause and 30 healthy controls were recruited in this study. Pure tone audiometric (PTA), transiently evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) of the study participants were analysed. At PTA, 6 and 8 kHz were lower in menopause group compared with both women with POF and controls. At TEOAE 3 and 4 kHz and at DPOAE 1, 2, 4 and 6 kHz were lower in menopause group compared with the controls. At DPOAE 6 kHz was lower in the POF group compared with the controls. Women with POF comparing to menopause group at TEOAE 3, 4 kHz and at DPOAE 4 and 6 kHz were lower in the menopause group. Inner ear function of both women in menopause and women with POF was declined compared to the healthy controls. Clinically, evaluation of hearing status may be considered in women with POF.Impact statementWhat is already known on this subject: Premature ovarian failure (POF) affects 1%-2% of women, and it adversely effects on health status (such as cardiovascular, psychological and cognitive disorders). Previous studies suggested that a lack of oestrogen might play a role in hearing disorders in women. However, we do not know POF's adversely effect on cochlea and hearing.What the results of this study add: The present study demonstrates that lower serum oestrogen has a negative effect hearing in women with POF at DPOAE 6 kHz.What the implications are of these findings for clinical practice and/or further research: The women with POF must be evaluated for hearing status.

Coronary artery calcification in middle-aged women with premature ovarian insufficiency.

OBJECTIVE: Women with premature ovarian insufficiency (POI) enter menopause before age 40. Early menopause was associated with increased risk for coronary artery disease (CAD), death from cardiovascular disease and all-cause mortality. We compared the prevalence of CAD between middle-aged women on average 10 years following the initial POI diagnosis, with a population-based cohort. DESIGN: Cross-sectional case-control study. PARTICIPANTS: Women from two Dutch University Medical Centers above 45 years of age previously diagnosed with POI (n = 98) were selected and compared with age- and race-matched controls from the Multi-Ethnic Study of Atherosclerosis (MESA). MEASUREMENTS: The primary outcome was detectable coronary artery calcium (CAC) determined by coronary computed tomography (CCT). RESULTS: Women with POI had significantly higher blood pressure, cholesterol and glucose, despite lower BMI compared to controls. Similar proportions of detectable CAC (CAC score >0 Agatston Units) were observed in women with POI and controls (POI n = 16 (16%), controls n = 52 (18%), P = 0.40 and Padj  = 0.93). In women with POI separately, we were not able to identify associations between CVD risk factors and CAC. The following CVD risk factors in controls were positively associated with CAC: age, diabetes mellitus, hypertension and LDL cholesterol. HRT use was negatively associated with CAC in controls. CONCLUSIONS: The presence of CAC did not differ significantly in women with POI around 50 years of age, compared to an age- and race-matched control group. We observe no increased calcified coronary disease in POI patients, despite the presence of unfavourable cardiovascular risk factors in these women.

A critical assessment of case reports describing absent uterus in subjects with oestrogen deficiency.

OBJECTIVE: The dual diagnosis of hypoplastic uterus in association with ovarian dysgenesis is regularly reported but the pathogenesis of the association is unclear. The uterus, however, may be invisible to all imaging modalities without at least six months of exogenous oestrogen exposure in complete ovarian failure. We assessed all available case reports in this category to estimate whether the apparent association between primary ovarian insufficiency or Turner syndrome and Mullerian agenesis can be largely accounted for by oestrogen deficiency. DESIGN: A literature review of all cases in which an association between ovarian insufficiency or Turner syndrome and hypoplastic uterus has been reported. PATIENTS: PubMed was searched for all case reports associated with relevant key terms. In total, 22 publications with a total of 25 patients were identified and reviewed; 14 subjects had the normal female karyotype (46,XX), and 11 subjects had Turner Syndrome. MEASUREMENTS: Proportion of subjects who had been exposed to adequate oestrogen prior to the absent uterine diagnosis. RESULTS: A diagnosis of absent uterus was made prior to exposure to exogenous oestrogen in 22/25 (88%) of subjects with primary hypogonadism including 14/14 females with normal karyotype and 8/11 females with Turner syndrome. CONCLUSIONS: Oestrogen deficiency is a possible explanation for most subjects being reported as having Mullerian agenesis in association with Turner syndrome or primary ovarian insufficiency. In the presence of oestrogen deficiency, no conclusion can be made about the status of the uterus until adequate exposure to exogenous oestrogen has been completed and we suggest reassessment of the uterus when full adult dose has been reached towards the end of induction of puberty.

Intrafamilial oocyte donation in classic galactosemia: ethical and societal aspects.

Classic galactosemia is a rare inherited disorder of galactose metabolism. Primary ovarian insufficiency (POI) with subfertility affects > 80% of female patients and is an important concern for patients and their parents. Healthcare providers are often consulted for subfertility treatment possibilities. An option brought up by the families is intrafamilial oocyte donation (mother-to-daughter or sister-to-sister). In addition to POI, galactosemia patients can also present varying cognitive and neurological impairments, which may not be fully clear at the time when mother-to-daughter oocyte donation is considered. Ethical and societal aspects arise when exploring this option. This study aimed to provide guidance in aspects to consider based on the views of different groups involved in the oocyte donation process. A qualitative study using in-depth semi-structured interviews with > 50 participants (patients, family members, and healthcare providers) was conducted. From these interviews, themes of concern emerged, which are illustrated and reviewed: (1) family relations, (2) medical impact, (3) patients' cognitive level, (4) agreements to be made in advance and organization of counseling, (5) disclosure to the child, and (6) need for follow-up. We conclude that discussing and carrying out intrafamilial oocyte donation in galactosemia patients requires carefully addressing these themes. This study adds value to the already existing recommendations on intrafamilial oocyte donation in general, since it highlights important additional aspects from the perspectives of patients and their families.