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

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.

Estrogen treatment in infertile women with premature ovarian insufficiency in transitional phase: a retrospective analysis.

PURPOSE: During the transitional phase of premature ovarian insufficiency (POI), sporadic resumption of ovulation is possible because of fluctuation of hormonal levels but the chance of spontaneous pregnancy is low, and the main perspective of childbearing in these women is egg donation or adoption. The purpose of the study was to verify whether treatment with estrogens in POI patients in transitional phase could reduce FSH levels and to evaluate if this pre-treatment could improve reproductive outcomes of in vitro fertilization (IVF). METHODS: Study patients (26) were administered with valerate estradiol 2 mg daily adding dihydrogesterone 10 mg daily during luteal phase for 3 months before IVF. Control group (26 patients) did not receive any pre-treatment. Ovarian stimulation was conducted in both groups with the same short GnRH-antagonist protocol. Clinical and laboratory data of patients were retrospectively analyzed. RESULTS: In the study group, 4/26 POI patients became spontaneously pregnant during pre-treatment. In the remaining patients, the mean level of FSH after the pre-treatment was significantly reduced compared with baseline. Levels of circulating estradiol on the day of hCG administration were significantly higher in the study group. The total number of MII oocytes retrieved and fertilized oocytes was significantly higher in the study group, as well as the number of embryos transferred for pickup and clinical pregnancy rate. CONCLUSIONS: Treatment with estrogens in infertile POI patients in transitional phase reduces circulating FSH levels, hence causing potential spontaneous conception. Moreover, in these patients, estrogen pre-treatment seems to improve IVF outcomes in a GnRH-antagonist short protocol compared to no pre-treatment.

The role of robotics in the management of endometriosis.

The advent of robot-assisted laparoscopy (RAL) is an important innovation which has provided new perspectives for the treatment of endometriosis, and particularly of deep infiltrating endometriosis (DIE). RAL offers several technical advantages in the treatment of this complex disease, such as 3D view, tremor filtration and better surgical ergonomics, thus improving surgical performances without no increase in surgical time, blood loss, and intra- or postoperative complications, while also reducing the rate of conversion to laparotomy. Additionally, thanks to its reduced learning curve compared to conventional laparoscopy (CL), it facilitates the training of less experienced surgeons. For these reasons, DIE might be one of the best indications for RAL in gynecologic surgery. However, very few retrospective studies and small cases series, and only one randomized clinical trial have been published in this regard. Further randomized control trials comparing CL to RAL for different stages of endometriosis and different procedures performed are warranted in order to be able to define potential benefits of RAL for endometriosis surgery.

A Novel System for Single-Port Laparoscopic Surgery: Preliminary Experience.

AIMS: To present preliminary data of single-access laparoscopic surgery with a new device for the treatment of benign adnexal pathologies. METHODS: Ten women with benign adnexal pathologies underwent salpingectomy (n = 4) and ovarian/para-ovarian cyst enucleation (n = 6) using a laparo-endoscopic single-port approach with an innovative advanced multiport reusable trocar inserted transumbilically through a small wound retractor. Trocar introduction time, operative time, estimated blood loss, conversion to standard laparoscopy, peri- and postoperative complications, hospital stay and Visual Analog Scale score (as assessment of pain and cosmesis) were analyzed. RESULTS: Port placement was successful in all patients. Mean trocar introduction time was 4.4 min (range 3.4-5.3 min) and no intra or postoperative complication occurred. The mean operating time was 50.0 ± 9.2 min and mean blood loss was 28.5 ± 8.8 ml. The mean hospital stay following surgery was 1.6 ± 0.5 days and convalescence was complete in 1 week. Neither scores for postoperative incisional pain nor cosmesis side effects have been observed in any subjects. CONCLUSION: We concluded that adnexal single-port surgery performed with this innovative advanced surgical instrumentation is a feasible, safe, and effective technique that drastically reduces postoperative pain and does not compromise cosmetic appearance. The isolation of the operative field by means of the drape prevents the contamination of the port site that occurs frequently, and mainly in adnexal pathologies of uncertain etiology. In addition, the ease of insertion and the conformation of the new port access also make the procedure feasible in obese patients.

Fertility-enhancing hysteroscopic surgery.

Anatomical uterine element and functional components play a fundamental role in the enhancing of fertility are the major actors. Uterine pathologies, including congenital or acquired lesions, have been reported in 21 to 47% of patients undergoing in vitro fertilization cycles. Hysteroscopy is an important procedure in the study of one of the most important element of fertility: the uterus, even if its use in the world of infertility is discussed. There are many studies on safety and feasibility of the procedure and on patient compliance, but there is no consensus on its systemic use. This study, thanks to the wide literature about the use of hysteroscopic surgery to enhance fertility in most of the congenital and acquired problems affecting women in fertility age, allows defining that diagnostic and operative hysteroscopy is a rapid and safety technology to improve fertility.

Different stimulation protocols for oocyte cryropreservation in oncological patients: a retrospective analysis of single university centre.

OBJECTIVE: To analyze the results obtain in cancer patients who receive the same controlled ovarian stimulation protocol, started in two different moments of the menstrual cycle, follicular or luteal phase. The stimulation is performed before cancer treatment in order to preserve fertility through oocytes cryopreservation. STUDY DESIGN: The study is a retrospective analysis about 25 cancer patients at our centre, Department of Reproductive Medicine of University of Pisa, in order to preserve their fertility before cancer treatment. Patients are divided into two groups depending on the menstrual cycle phase, follicular or luteal phase, at the moment of first examination. Standard stimulation protocol with gonadotropins is administered in the follicular group, whereas in the second group we use GnRH (gonadotropin-releasing hormone) antagonist before gonadotropins administration in order to have a rapid luteolysis. The outcome measures are the number of days needed before starting procedure, duration of stimulation, cumulative dosage of gonadotropins number of oocyte retrieved and percentage of mature oocytes. RESULTS: Any difference showed between two groups based on days of stimulation, total amount of gonadotropins administered and the number of good mature quality oocytes was retrieved. The real difference is the number of days needed to start the procedure, lesser in the luteal group. CONCLUSIONS: This study suggests that oocytes can be obtained before cancer treatment, irrespective of menstrual cycle phase without compromising the efficacy of procedure. Moreover, starting ovarian stimulation anytime during menstrual cycle allows the patients to not postpone the beginning of cancer treatment. Different stimulation protocols, according to different kinds of disease, are available in order to obtain the maximum results without any complication for patients.

Comparison of the initial surgical experience with robotic and laparoscopic myomectomy.

OBJECTIVE: To compare the initial surgical outcomes of robotic and laparoscopic myomectomy in patients with symptomatic uterine myomas. STUDY DESIGN: Retrospective chart review of 86 patients undergoing robotic (RM) (n = 43) or laparoscopic (LM) (n = 43) myomectomy. Data included fibroid characteristics (number, weight, location) layers of uterine reconstruction, operating time, blood loss, complications, and postoperative hospital stay. RESULTS: No significant differences were noted between RM and LM for fibroid number and weight and mean operating time, although the number of patients receiving at least a double-layer uterine reconstruction was higher in RM than LM. Blood loss was higher after LM, while no differences resulted in hospital stay. CONCLUSION: RM may have some additional advantages compared with LM in terms of bleeding and uterine suturing without compromising operation duration, at least when surgeons were at the beginning of their experience of endoscopic treatment of symptomatic uterine myomas.

Infertility and pregnancy loss in euthyroid women with thyroid autoimmunity.

Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 5-20% of women during the age of fertility. Prevalence of thyroid autoimmunity is significantly higher among infertile women, especially when the cause of infertility is endometriosis or polycystic ovary syndrome. Presence of thyroid autoimmunity does not interfere with normal embryo implantation and have been observed comparable pregnancy rates after assisted reproduction techniques in patients with or without thyroid autoimmunity. Instead, the risk of early miscarriage is substantially raised with the presence of thyroid autoimmunity, even if there was a condition of euthyroidism before pregnancy. Furthermore the controlled ovarian hyperstimulation, used as preparation for assisted reproduction techniques, can severely impair thyroid function increasing circulating estrogen levels. Systematic screening for thyroid disorders in women with a female cause of infertility is controversial but might be important to detect thyroid autoimmunity before to use assisted reproduction techniques and to follow-up these parameters in these patients after controlled ovarian hyperstimulation and during pregnancy.

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.

Follicular fluid VEGF levels directly correlate with perifollicular blood flow in normoresponder patients undergoing IVF.

BACKGROUND: It has become increasingly clear that the follicular microenvironment of the maturing human oocyte is a determining factor for the implantation potential of an embryo deriving from that oocyte. Indeed the quality and maturity of an oocyte are influenced by the level of intrafollicular oxygen content which, in turn, is proportional to the degree of follicular vascularity. The aim of the study was to establish whether there is a relationship between follicular fluid VEGF concentrations, perifollicular vascularity and reproductive outcome in normal responders under the age of 35 undergoing IVF. MATERIALS AND METHODS: Sixty-one consecutive patients, all at their first IVF cycle, were included in the study. All patients had primary infertility due to male factor or tubal factor. At oocyte retrieval, the perifollicular vascularity of two follicles per ovary was estimated qualitatively through power Doppler blood flow, for a total of two hundred forty-four follicles. The follicular fluid from the identified follicles was centrifuged and stored until VEGF assay. The maturity and fertilization rate of the corresponding oocytes as well as embryo quality and pregnancy rate were recorded. RESULTS: In our study, we found VEGF levels to be significantly correlated with grade of perifollicular vascularity. Oocytes obtained from follicles with the higher grade of vascularization also showed a higher rate of fertilization, embryos, a better quality and higher pregnancy rates were obtained in women with highly vascularized follicles. Perifollicular blood flow doppler indices seem to predict oocyte viability and quality. Moreover, VEGF may play a potential role in the development of the perifollicular capillary network. DISCUSSION: The ability of a given follicle to express VEGF and develop an adequate vascular network may be inter-related in patients under the age of 35. An adequate blood supply may be fundamental important in the regulation of intrafollicular oxygen levels and the determination of oocyte quality.

Vascular endothelial growth factor level changes during human embryo development in culture medium.

OBJECTIVE: Implantation is a complex phenomenon consisting of the first strong contact between embryo and endometrium. Recent studies have demonstrated that this process is dependent not only on the 'readiness' of the endometrium, but also on complex interactions between endometrial and embryonic tissues that cross-talk by means of different molecules (growth factors, cytokines, vasoactive factors). Investigations performed on human blastocysts indicate a role for vascular endothelial growth factor (VEGF) in these processes. The aim of the present study was to investigate VEGF levels at different stages in human embryo culture medium. STUDY DESIGN: We selected 20 women among patients undergoing assisted reproduction with the in vitro fertilization-blastocyst transfer protocol. The oocytes were inseminated by intracytoplasmic sperm injection. For each patient, approximately two cultures of four microinjected oocytes (and then of four embryos) were performed. Each culture of four oocytes/embryos was placed in one dish to increase the probability to detect small VEGF concentrations. RESULTS: Results showed significantly higher VEGF levels in the medium at blastocyst stage (12.16 +/- 2.80 pg/ml) compared with embryos at pronuclear stage (13.58 +/- 2.32 pg/ml) and microinjected oocytes (12.80 +/- 3.45 pg/ml). CONCLUSIONS: An important VEGF synthesis by blastocysts occurs during human embryo development.