Resumption of Ovarian Function and Pregnancies in 358 Patients with Premature Ovarian Failure
ABSTRACT Resumption of ovarian activity and spontaneous pregnancies are described in patients with premature ovarian failure (POF), but there is a lack of data concerning the prevalence of and predictive factors for these phenomena.
The aim of the study was to determine both the prevalence of and predictive factors for spontaneous resumption of ovarian function in POF patients.
A mixed retrospective and prospective study was performed at a referral center for reproductive endocrinology.
A total of 358 consecutive POF patients were followed from 1997 to 2010 in our center.
The cumulative incidence of resumption of ovarian function was determined, and predictive factors were identified by univariate and multivariate analysis.
Of 358 patients with idiopathic POF, 86 (24%) patients presented features indicating resumption of ovarian function, and in 77 cases (88%) within 1 yr of diagnosis. Twenty-one spontaneous pregnancies (16 births, five miscarriages) occurred in 15 (4.4%) patients. Multivariate analysis (Cox model) showed that a familial history of POF, secondary amenorrhea, presence of follicles at ultrasound, and inhibin B and estradiol levels were significantly predictive of resumption of ovarian function (P < 0.01), whereas association with an autoimmune disease, anti-mullerian hormone level, the presence of follicles on biopsy, and/or genetic abnormalities did not appear predictive. We created a predictive score for resumption of ovarian function comprising age at diagnosis, presence of follicles at ultrasound, and inhibin B level.
Intermittent ovarian activity in patients with POF is not a rare phenomenon. The predictive score described in this study may help us to identify POF patients most likely to recover intermittent ovarian function.
SourceAvailable from: Carmen Messerlian[Show abstract] [Hide abstract]
ABSTRACT: To estimate the risk of preterm birth in singleton infants conceived through low-technology assisted reproduction (intrauterine insemination and/or ovulation induction/stimulation). Hospital-based cohort study. University-affiliated hospital. Singleton babies born between 2001 and 2007 to 16,712 couples with no reported infertility (reference category), 378 babies conceived with low-technology treatment; 437 conceived with high-technology treatment; and 620 conceived naturally after a period of infertility. None. Treatment data were obtained from couples undergoing standard infertility investigation and care. Preterm birth, defined at three clinical endpoints: <37, <35, and <32 weeks of completed gestation. After adjustment for age, parity, education, smoking, alcohol/drug use, and body mass index, the risk ratios and 95% confidence intervals (CI) of preterm birth for low technology were: 1.49 (CI: 1.12-2.00); 2.02 (CI: 1.30-3.13); and 2.93 (CI: 1.63-5.26) at <37, <35, and <32 weeks gestation, respectively, not dissimilar from the estimates for in vitro fertilization. Restricting the analysis to primiparas strengthened the association between treatment and preterm birth at the lower gestational endpoints. The increased risk persisted when the untreated group was used as the reference category, although the estimates were attenuated. In this large hospital-based cohort study, low-technology assisted reproduction appeared to be a moderately strong predictor of preterm birth, with similar associations observed in the high-technology treatment group. After adjusting for confounders, as well as the shared characteristics of infertile couples, associations were attenuated but remained significant, suggesting that part of the risk is likely attributable to the treatment. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.Fertility and Sterility 11/2014; 103(1). DOI:10.1016/j.fertnstert.2014.10.006 · 4.30 Impact Factor
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ABSTRACT: Although hormonal regulation of ovarian follicle development has been extensively investigated, most studies concentrate on the development of early antral follicles to the preovulatory stage, leading to the successful use of exogenous FSH for infertility treatment. Accumulating data indicate that preantral follicles are under stringent regulation by FSH and local intra-ovarian factors, thus providing the possibility to develop new therapeutic approaches. Granulosa cell-derived C-type natriuretic factor (CNP) not only suppresses the final maturation of oocytes to undergo germinal vesicle breakdown before ovulation but also promotes preantral and antral follicle growth. In addition, several oocyte-and granulosa cell-derived factors stimulate preantral follicle growth by acting through WNT, receptor tyrosine kinase, receptor serine kinase, and other signaling pathways. In contrast, the ovarian Hippo signaling pathway constrains follicle growth and disruption of Hippo signaling promotes the secretion of downstream CCN growth factors capable of promoting follicle growth. Although the exact hormonal factors involved in primordial follicle activation has yet to be elucidated, the AKT and mTOR signaling pathways are important for the activation of dormant primordial follicles. Hippo signaling disruption following ovarian fragmentation, combined with treating ovarian fragments with PTEN inhibitors and phosphoinositide-3-kinase stimulators to augment AKT signaling, promote the growth of preantral follicles in patients with primary ovarian insufficiency (POI), leading to a new infertility intervention for such patients. Elucidation of intraovarian mechanisms underlying early folliculogenesis may allow the development of novel therapeutic strategies for patients diagnosed with POI, polycystic ovary syndrome (PCOS), and poor ovarian response to FSH stimulation, as well as for infertile women of advanced reproductive age.Endocrine Reviews 09/2014; 36(1):er20141020. DOI:10.1210/er.2014-1020 · 19.36 Impact Factor
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ABSTRACT: The cause of the primary ovarian insufficiency (POI) remains unknown in the majority of cases. A retrospective study was carried out in 17 girls with POI and normal 46,XX karyotype evaluated before 20 years of age. The etiology of POI was determined in eight girls (group 1) and remained idiopathic in nine girls (group 2). In group 1, five patients had a medical history: cerebellar ataxia due to congenital disorder of glycosylation (CDG) 1 in three cases, mitochondrial disease in one case, and autoimmune deficiencies in one case. The diagnosis of POI was made on pubertal delay or primary amenorrhea in these five patients, whilst the others presented with clitoral hypertrophy at birth or short stature and pubertal delay in two cases with NR5A1 mutation or with short stature and learning difficulties in one case with mitochondrial disease. In group 2, associated diseases were arthrogryposis malformative, gut, and bladder malformations and kidney failure or parieto-occipital tumor. The genes tested (NR5A1, BMP15, GDF9, and NOBOX) showed no mutation. Conclusions: The frequency of defined etiologies (47 %) is high. This is probably because of the recruitment of the cases at the pediatric center, where other somatic anomalies can lead to the accurate determination of the etiology.European Journal of Pediatrics 11/2014; DOI:10.1007/s00431-014-2457-5 · 1.98 Impact Factor