Early Premature Ovarian Insufficiency Research Articles

Premature ovarian insufficiency

Key content: Premature ovarian insufficiency (POI) is a clinical syndrome involving ovarian follicle depletion and defined by loss of ovarian function before 40 years of age. The diagnostic workup in women with suspected POI is in two steps: confirming the diagnosis and establishing its cause; it is important to understand the rationale for performing each diagnostic test, how to interpret results and appropriate multidisciplinary team involvement. Treatment options include various regimens and preparations of hormone replacement therapy (HRT), monitoring and surveillance, induction of puberty in those with very early POI, complimentary treatment and fertility treatment. Management of POI requires a comprehensive and personalised strategy that addresses not only the physical symptoms and disease risks, but also the psychosocial and reproductive health aspects, and it is important that women receive adequate counselling. Learning objectives: To raise awareness of early diagnosis of POI. To be able to discuss the implications of POI for the health of women affected and their families, as well as for different hormonal and non‐hormonal treatment options. To understand various fertility treatment options for POI. Ethical issues: It is important to consider the reproductive and diagnostic implications for women with chromosomal or genetic problems (e.g. Turner syndrome, Fragile X mutation carriers) and for their family members. A diagnosis of POI may have differing implications based on social and cultural factors, and healthcare providers should consider a patient's values, beliefs, cultural background and preferences.

P-637 Evaluation of a digitally integrated ovulation prediction kit with proof of ovulation – a pilot study

Abstract Study question Is a digital ovulation prediction kit (OPK) with integrated progesterone measurements a useful tool in predicting and proving ovulation? Summary answer The digitally integrated OPK with progesterone integration may be a helpful tool for couples to identify the woman’s fertile window and detect anovulation. What is known already Apart from detecting the coming fertile window (i.e. the period of the highest probability of conception during the menstrual cycle, including the 5 days previous to and the day of ovulation itself), knowledge whether the likely ovulation indeed occurs, is crucial for achieving pregnancy. As women’s hormone profiles show intra- and interindividual variations, an individual prediction of the fertile window is a promising approach for couples, particularly in early premature ovarian insufficiency and perimenopause. Information whether the presumed ovulation has actually happened is not provided by most cycle apps. Study design, size, duration Healthy women, aged 21 to 44 years, who had not been taking hormonal contraceptives for at least three months were recruited via social media, paper postings and hand-outs. Women with infertility for more than 24 months were excluded. Up to three cycles were measured in every woman in case of a lacking pregnancy. Participants/materials, setting, methods Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) in first morning urine were gaged via lateral flow immunoassay test strips (LFIA) (RunBio Biotechnology Ltd.). Three algorithms of the smartphone application Pearl Fertility (iOS 1.0.3-1.0.5, Colorimetrix GmbH) were applied to predict the day of ovulation. Photographic visual control of the LH test strips, vaginal ultrasound close to the predicted ovulation and progesterone (PdG LFIA) were used to confirm ovulation, human chorionic gonadotropin (HCG LIFA) to confirm pregnancy. Main results and the role of chance 36 cycles of 19 women recruited for this pilot study were started. 6 participants dropped out or were excluded, leaving 25 evaluable cycles in 13 healthy women, average age 37 years (range 30 to 44), who had not been taking hormonal contraceptives for at least three months. 76 % of the analysable cycles had corresponding prediction of ovulation by algorithm and by visual control of the measured maximum value of LH (OVV). OVV corresponded with the day of ovulation determined retrospectively by length of luteal phase in 75 % (Bland-Altman plot (acceptable deviation Δ≤|2| days)). Prediction of ovulation differed by 2.12±3.13 days (mean±SD) between OVV and prospective cycle-length-based data (Wilcoxon signed-rank test (p < 0,05)). The PdG LIFA suggested ovulation in 84 % of the cycles with presumed ovulation by postovulatory PdG measurement. 6 of the participating women got pregnant during the study. Analysis of cumulative rate of pregnancy with 95 % confidence interval resulted in 25±21 %, 40±19 % and 40±17 % within the first, second and third cycle. Limitations, reasons for caution In order to make valid statements about the benefit of digitally integrated OPKs, further research with a larger population is needed. Perimenopausal women and patients with irregular cycles may specifically benefit from individual self-monitoring. Wider implications of the findings The knowledge of the fertile window is expected to help fertile couples to achieve pregnancy and proof of ovulation or anovulation may detect infertility due to anovulation sooner, thereby reducing the interval until diagnosis and treatment. Trial registration number 'not applicable'

Ovarian Reserve Markers in Premature Ovarian Insufficiency: Within Different Clinical Stages and Different Etiologies.

ObjectiveTo characterize the ovarian reserve indicators for premature ovarian insufficiency (POI) at different disease stages and with various etiologies.MethodsAccording to different FSH levels and menstrual conditions, patients with normal ovarian reserve (NOR with 5 IU/L<FSH<10 IU/L, n=987), precursor stage of POI (pre-POI with 10 IU/L<FSH ≤ 25 IU/L, n=410), early POI (25 IU/L<FSH ≤ 40 IU/L n=147), and premature ovarian failure (POF with FSH>40 IU/L, n=454) were retrospectively screened and their records were abstracted from Reproductive Hospital Affiliated to Shandong University between 2014 and 2019. Based on the known etiologies, POI patients were subdivided into genetic, iatrogenic, autoimmune and idiopathic subsets according to the known etiologies. The phenotypic features were compared within different subgroups, and the predictive value of ovarian reserve markers was analyzed.ResultsThe ovarian reserve indicators consecutively deteriorated with the progress of ovarian insufficiency, indicated as an increase of FSH and LH but decrease of AMH, inhibin B, AFC, E2 and T (P<0.01). Most of them changed significantly from NOR to pre-POI while remained relatively stable at a low level or even undetectable at early POI and POF stage. AMH showed the highest predictive value for pre-POI (AUC 0.932, 95% CI 0.918-0.945) and POI (AUC 0.944, 95% CI 0.933-0.954), and the combination of AMH and AFC was highly promising for early prediction. Additionally, significant differences existed in AMH, inhibin B and AFC among women with different etiologies of POI (P<0.05), and the genetic POI presented the worst hormone status.ConclusionsOur study indicated a high heterogeneity of POI in both endocrine hormones and etiological phenotypes. The quantitative changes and cutoff values of AMH and AFC could provide new insights in the prediction and early diagnosis of POI.

Gonadotropin-releasing hormone agonists for the protection of ovarian function in premenopausal patients treated by chemotherapy: a meta-analysis

Objective To evaluate systematically the effectiveness of gonadotropin-releasing hormone agonist (GnRHa) administration before chemotherapy and/or during chemotherapy for the protection of ovarian function in premenopausal women. Methods PubMed, Cochrane Library, Medline, Embase, China Biomedical Literature Database, CNKI were searched to collect the clinical randomized control trail (RCT) of ovarian function protection in premenopausal women receiving chemotherapy by using GnRHa. RevMan5.3 software was used to analyze the incidence of early premature ovarian insufficiency (POI), menstrual recovery rate, pregnancy rate and other indicators. Results A total of 12 articles were included, including a total of 1 509 premenopausal women who received chemotherapy for malignant diseases. GnRHa combined with chemotherapy reduced the incidence of POI (OR = 0.36, 95% CI 0.23-0.56, P < 0.01) and improved the menstrual recovery rate during follow-up (OR = 2.49, 95% CI 1.72-3.60, P < 0.01). GnRHa combined with chemotherapy could increase the pregnancy rate of patients aged 35 years and older (OR = 2.04, 95% CI 1.08-3.83, P = 0.03). Conclusion GnRHa administration before chemotherapy and/or during chemotherapy may prevent the chemotherapy damage to ovarian function, reduce the incidence of POI, and improve the recovery rate of menstruation. Key words: Ovarian function protection; Gonadotropin-releasing hormone agonist; Drug therapy; Premature ovarian insufficiency; Meta-analysis

Utility of complete blood count parameters to detect premature ovarian insufficiency in cases with oligomenorrhea/amenorrhea.

There are very few biomarkers available to diagnose cases with premature ovarian failure. Some complete blood count parameters have been introduced to be diagnostic biomarkers for several disorders associated with inflammatory process. Due to the evidence that indicated chronic inflammatory process to be underlying pathophysiology in premature ovarian insufficiency (POI), we aimed to assess the predictive value of complete blood count parameters for POI diagnosis. A total of 96 women diagnosed to have premature ovarian failure were compared with 110 otherwise healthy women in terms of some basal hormone levels and complete blood count parameters. Mean age was similar between groups. Neutrophil/lymphocyte and mean platelet volume/lymphocyte ratios were significantly higher in group with POI (P<.001, P<.003, respectively). In group with POI, there were significant correlations between anti-Mullerian hormone and follicle stimulating hormone (r=-.30, P<.05), anti-Mullerian hormone and white blood cell count (r=.23, P<.05). Mean platelet volume/lymphocyte ratio significantly predicted cases with POI (AUC=0.607, %95 CI: 0.529-0.684; P<.001). Neutrophil/lymphocyte and mean platelet volume/lymphocyte ratios are elevated in POI. There have been some controversies about the value of neutrophil/lymphocyte in POI diagnosis. We suggest mean platelet volume/lymphocyte ratio as a new biomarker in early POI because it is cheap and easily accessible compared to anti-Mullerian hormone.