Sara Pinelli

DHEA supplementation improves follicular microenviroment in poor responder patients

Objective: To analyze the effect of dehydroepiandrosterone (DHEA) supplementation on follicular microenvironment and on in vitro fertilization (IVF) outcomes among poor responder patients. Study design: We enrolled 24 patients diagnosed as poor responders based on ESHRE consensus criteria. One group received 25 mg/die three times daily of DHEA supplementation for 3 months previous to IVF cycle, while the other did not receive any treatment. COH was performed with rFSH and hMG, and a GnRH antagonist was administered according to a flexible protocol. We evaluated perifollicular vascularization of recruited follicles through power Doppler blood flow analysis and follicles were graded as described by Chui et al. Follicular fluids (FF) from F3-F4 follicles were collected, and FF levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor1 (HIF1) were measured. Results: FF levels of HIF1 were statistically significant lower in women treated with DHEA (14.76 ± 51.13 vs. 270.03 ± 262.18 pg/ml; p = 0.002). On the contrary, VEGF levels did not differ between the two groups. Concerning COH, in the DHEA-group the mean duration of treatment was significantly shorter (9.83 ± 1.85 vs. 12.09 ± 2.81; p = 0.023). Total numbers of oocytes retrieved, fertilized oocytes, good quality embryos, number of transferred embryos and clinical pregnancies tended to be higher in study group, but the results were not significant. On the other hand, considering the oocytes retrieved in selected F3-F4 follicles, there was a relation between HIF1 levels and oocytes quality. In fact, mature oocytes retrieved in selected follicles were significantly more numerous in DHEA-group (0.50 ± 0.52 vs. 0.08 ± 0.29; p = 0.018). Conclusions: The improvement of reproductive parameters after DHEA supplementation in poor responders may be explained through the effect that this pro-hormone exerts on follicular microenvironment.

Conventional IVF as a laboratory strategy to rescue fertility potential in severe poor responder patients: the impact of reproductive aging.

Abstract Objective: To investigate whether laboratory strategies can improve in vitro fertilization (IVF) outcome in poor responder patients. We compared the effectiveness of conventional IVF and intra cytoplasmic sperm injection (ICSI) in assisted reproductive technologies cycles in which only one or two oocytes were retrieved at ovarian pick up, in the absence of male infertility. Design: Retrospective analysis of 425 cycles in 386 poor responder patients. Intervention(s): Standard stimulation protocol with gonadotropins and gonadotropin releasing hormone (GnRH) antagonist. Main outcome measure(s): Fertilization rate, cleavage rate, good-quality embryo rate, implantation rate, clinical pregnancy rate (PR) and miscarriage rate. Results: IVF was found to be more advantageous for implantation and PR, especially in patients under 35 years and in women aged between 35 and 38 years. No differences were noted in the other parameter evaluated. Patients aged over 38 years showed no difference using the two techniques. Conclusion: The employment of ICSI in the absence of a male factor can reduce reproductive outcome in poor responder. Probably because of aging-related defects overcoming the advantage of sperm selection, the choice of IVF technique is not relevant to reproductive success when oocyte quality is compromised by reproductive aging. Although further randomized trials are needed to confirm our results, we propose that, in absence of male infertility, conventional IVF might be the technique of choice in young patients, especially in those aged below 35 years.

Ovarian response to controlled ovarian stimulation in women with different polycystic ovary syndrome phenotypes

Abstract Controlled ovarian stimulation (COH) in PCOS is a challenge for fertility expert both ovarian hyperstimulation syndrome (OHSS) and oocytes immaturity are the two major complication. Ovarian response to COH vary widely among POCS patients and while some patients are more likely to show resistance to COH, other experienced an exaggerated response. The aim of our study is to investigate a possible correlation between PCOS phenotypes and the variety of ovarian response to COH and ART outcomes in patients with different PCOS phenotypes. We retrospectively analyzed a total of 71 cycles performed in 44 PCOS infertile patients attending ART at Centre of Infertility and Assisted Reproduction of Pisa University between January 2013 and January 2016. Patientsundergoing IVF with GnRH-antagonist protocol and 150–225 UI/days of recombinant FSH; triggering was carried out using 250 mg of recombinant hCG or a GnRH analogous on the basis of the risk to OHSS. We observed that Phenotype B had a tendency to have a greater doses of gonadotropins used respect to all phenotypes. Phenotype A group showed a greater serum estrogen levels compared to all phenotypes groups, a greater number of follicles of diameter between 8–12 mm found by ultrasound on the day of triggering and a greater mean number of freeze embryo. Additionally serum AMH and antral follicles count (AFC) follow the same trend in the different phenotypes ad they were significantly higher in phenotype A and in phenotype D. In conclusion this study shows that the features of PCOS phenotypes reflect the variety of ovarian response to COH as well as the risks to develop OHSS. Serum AMH and AFC are related to the degree of ovulatory dysfunction making these ‘added values’ in identifying the different PCOS phenotypes. Phenotype A seems to be the phenotype with the higher risk to develop OHSS and the use of GnRH as a trigger seems to improve oocyte quality. To classify PCOS phenotype at diagnosis might help clinicians to identify patients at greater risk of OHSS, customize therapy and subsequently plan the trigger agent.

Management of sexual dysfunction due to vulvar lichen sclerosus in postmenopausal women

Lichen sclerosus is a chronic skin disease, probably immune‐mediated, with a strong genetic component. It shows a predilection for external genitalia. It is most common in postmenopausal women, although it has been documented at all ages and in both sexes. The exact prevalence of lichen sclerosus is unknown. However, in recent years much progress has been made in defining its etiology and epidemiology, and we now know that it is far more frequent than previously thought. The purpose of this review is to focus more attention on the relationship between LS and sexual dysfunction, and on a few important aspects of managing perimenopausal patients diagnosed with LS. Lichen sclerosus is a chronic, debilitating condition that may progress to cause significant physical and psychological complications. The disease calls for lifetime follow‐up.

PCOS and pregnancy: a review of available therapies to improve the outcome of pregnancy in women with polycystic ovary syndrome

ABSTRACT Introduction: Polycystic ovary syndrome (PCOS) is a common cause of female infertility affecting multiple aspects of a women’s health. Areas covered: The aim of this review is to summarize the existing evidence on the treatment of PCOS patients and to examine the actual available therapies to overcome the problem of infertility and improve the outcome of pregnancy. We analyse different treatment strategies such as lifestyle modification, bariatric surgery, insulin sensitizing agents, inositol, clomiphene citrate (CC), aromatase inhibitors, gonadotrophins, laparoscopic ovarian drilling, and assisted reproductive techniques (ART). Expert commentary: Lifestyle modification is the best initial management for obese PCOS patients seeking pregnancy and insulin sensitizing agents seem to have an important role in treating insulin resistance. Up to now, CC maintains a central role in the induction of ovulation and it has been confirmed as the first-line treatment; the use of gonadotrophins is considered the second-line in CC resistant patients; laparoscopic ovarian drilling is an alternative to gonadotrophins in patients who need laparoscopy for another reason. However, in anovulatory patients, ART represents the only possible alternative to obtain pregnancy. Larger and well-designed studies are needed to clarify the best way to improve the outcome of pregnancy in PCOS women.

Association between Helicobacter pylori infection and vulvar lichen sclerosus: a clinical comparative study

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

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.

Cathecol-O-methyltransferase inhibitors: another possibly useful pharmacological tool for treating Parkinson’s disease in pregnancy?

Experience on the effects of pregnancy on Parkinson’s disease (PD) and vice versa is scarce (Schrag and Schott 2006). In addition, there is controversy in the literature about neurological symptoms control, with various obstetrical outcomes. Nowadays, as women increasingly delay childbearing, and PD being an age-related disease, the prevalence of pregnant women with PD is likely to rise. The report of using a new medication would therefore provide additional information for practicing clinicians looking after pregnant women with PD. Medical schedules described during pregnancy include Levodopa/Carbidopa or Levodopa/Benserazide, also combined with dopamine agonists, Amantadine, Selegeline or dopamine agonist monotherapy (Schrag and Schott 2006). The United States of America Food and Drug Administration lists antiparkinsonian drugs in pregnancy category C. Category C means either: (1) studies on animals have shown potential risk to the foetus, (2) no well-controlled studies in humans have yet been published, (3) studies on humans and animals are unavailable. Regarding Entacapone, small animal reproduction studies have shown a teratogenic effect on the foetus and there are no adequate and well-controlled studies in humans (Hagell et al. 1998). Consequently, even if the real risk to human foetuses is unknown, potential benefits to the mother in terms of disease control may outweigh the potential risks to the foetus (Schrag and Schott 2006; Kranick et al. 2010). No major obstetrical complications have been reported on the use of Levodopa plus Carbidopa or Benserazide during pregnancy, whereas Amantadine has been associated with cardiovascular teratogenicity (Schrag and Schott 2006; Robottom et al. 2008; Kranick et al. 2010). The main published complications potentially linked to PD treatment during pregnancy are first-trimester spotting and spontaneous miscarriage, nausea and vomiting, as exhaustively reviewed by Hagell et al. (1998). This paper reports the case of a pregnant woman affected by early onset PD treated successfully with Levodopa, Carbidopa, and Entacapone, a Cathecol-O-MethylTransferase (COMT) inhibitor. Entacapone is a peripheral inhibitor of COMT, which reduces dyskinesias and motor fluctuations associated with degradation of Levodopa in the peripheral nervous system, contrasting the progressive shortening in the duration of Levodopa action described as ‘wearing off’ (Najib 2001). The main adverse events reported in patients assuming Entacapone are dopaminergic effects related to Levodopa increased bioavailability. These include involuntary movements and nausea that can be easily managed by decreasing the dosage of Levodopa. Main non-dopaminergic side effects are diarrhoea and abdominal pain (Schrag 2005).

Successful treatment of total obliteration of vulva caused by inveterate vulvar lichen sclerosus

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Association between HCV infection and cutaneous-mucosal lichen planus: an update

329 Patient 2 did not develop gastrointestinal disorders and infectious diseases were limited; the patient is still alive at eight years old, which may make her the oldest surviving patient. However, her current condition is very poor, with hyaline deposits in several tissues and the appearance of tumour nodules all over her body. To date, there is no specific treatment for ISH. Management of pain, physiotherapy, and nutritional support may help patients to improve their quality of life. ISH has a very poor prognosis [8-10]. All published cases died before three years due to recurrent chest infections. The novelty of our case series is the prolonged survival of Case 2. This child, who is now eight years old and still alive, is the oldest case of ISH so far published in the literature. In summary, the challenge in ISH is early diagnosis. The identification of mutations in CMG2 makes DNA-based prenatal diagnosis feasible for subsequent pregnancies.