Hysteroscopic findings in chronic endometritis.

Chronic endometritis (CE) is a subtle pathology. Despite being difficult to detect and probably underdiagnosed, it has great clinical relevance, representing as it does a reversible cause of infertility. Nowadays, histological examination with identification of endometrial stromal plasma cells is considered the gold standard for diagnosis. Diagnostic difficulties persist, however, as a result of the technical limitations of this method and the lack of standardized histological diagnostic criteria. Hysteroscopy has been proposed as an aid for CE diagnosis. The method works by detecting signs of inflammation (focal or diffuse hyperemia, stromal edema, presence of micropolyps and the typical strawberry aspect) on the endometrial surface. Yet, the jury is still out on how reliable this technique is. Hysteroscopy displays a high sensitivity (over 86% and up to 100%) and high negative predictive value (over 92% and up to 100%) in the diagnosis of CE, and it should probably be performed routinely in the assessment of patients with unexplained infertility, repeated implantation failure and repeated pregnancy loss; however, since values in the literature regarding specificity are conflicting, in cases of suspected CE, hysteroscopy may be combined with histological examination, which remains the gold standard to confirm CE. Considering that histopathological evaluation probably underdiagnoses CE, and that hysteroscopy tends to overdiagnose, further studies are needed to determine which technique (or combination of techniques) has greater value for patients.

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.

Genetic conditions impairing female fertility.

Fertility represents a biological and psychological requirement for women. Some genetic diseases represent a rare cause of infertility, being responsible for 10% of cases of premature ovarian insufficiency. Among these, the most frequent and also those most studied by researchers are Turner Syndrome - due to a karyotype abnormality of the X chromosome pair - and the presence of fragile X premutation (FMR1). To exclude these conditions the diagnostic workup for non-iatrogenic premature ovarian insufficiency (POI) involves the performance of a karyotype analysis and the search for the FMR1 gene mutation, as well as the search for the presence of Y-chromosomal material. However, several other mutations and genetic syndromes associated with POI development have recently been highlighted, although they occur rarely, such as the GALT gene mutation in galactosemia or the FOXL2 gene mutation in BPES and many others, and further autosomal genetic testing are indicated if clinical suspicion is present. Mutations of BRCA 1 and 2 genes, make patients at genetically determined high risk of developing early ovarian or breast cancer and of getting POIs for the treatments they must undergo to prevent it (prophylactic bilateral oophorectomy) or treat it (chemotherapy). The management of impaired fertility is not less important than that of other syndromic manifestations for the quality of life of patients. Few data are available regarding the efficiency of cryopreservation of reproductive material (oocytes, embryos or ovarian tissue) in order to preserve fertility in this particular subgroup of patients, but certainly it represents a promising chance and a hope for the future.

Ovarian Reserve Markers to Identify Poor Responders in the Context of Poseidon Classification.

It is well-known that poor ovarian reserve is a cause of infertility, poor response to gonadotrophin stimulation and poor success rate after in vitro fertilization (IVF) cycles. Some years ago a consensus was elaborated on precise criteria which can lead to a correct identification of poor responders (the Bologna criteria). More recently, the POSEIDON group has proposed a new stratified classification of patients with low prognosis, also with the aim of providing clinical indications for the management of these patients. A literature search was carried out for studies that investigated the ability of ovarian reserve markers, in particular AMH and AFC, to predict poor ovarian response in IVF cycles; secondly, studies regarding the Bologna criteria and their prognostic value were analyzed and available literature on POSEIDON classification was reported. The most recent markers of ovarian reserve (serum AMH and ultrasound AFC) have shown to provide a direct and accurate measurement of ovarian follicle pool. These markers have generally shown comparable predictive power for ovarian response and a number of retrieved oocytes in IVF cycles. "Abnormal ovarian reserve test" is a very important parameter both in the Bologna criteria and in the POSEIDON classification. Several studies have already been published about the reproductive outcome of patients defined as poor responders according to the ESHRE Bologna criteria: all of them agree on the poor IVF outcome and low pregnancy rate of these patients. Instead, being the POSEIDON classification of very recent publication, the efficacy of the POSEIDON approach in improving management and outcomes of POR patients has yet to be tested and validated with future prospective clinical trials. Prediction of poor response may help clinicians choose the stimulation protocol with the aim of gaining patient compliance and cost reduction, and many efforts have been made by researchers in this sense, including the formulation of the Bologna criteria and of the POSEIDON classification, in which the ovarian reserve markers (AMH and AFC) play a fundamental role.