Paola Persico

Polar body morphology and spindle imaging as predictors of oocyte quality

It has been suggested that first polar body (PBI) morphology reflects oocyte competence. Oocytes with an intact normal-sized PBI have been described as generating better day 2 embryos, higher blastocyst yield, and increased pregnancy and implantation rates. In other studies, PBI morphology was found to be unrelated to fertilization rate, embryo quality, and blastocyst formation. In a prospective analysis, the predictive value of the PBI was investigated by comparing the development of oocytes retrieved from intracytoplasmic sperm injection patients and displaying different PBI morphology, classified according to the following characteristics: normal size and smooth surface (I), fragmented (II), rough surface (III), or large size (IV). Fertilization rates were 59, 57, 64 and 60% respectively. No significant differences were found between the various groups. The proportions of high quality (grade A) day 2 embryos were also comparable among groups I-III (14, 12 and 17% respectively), while the low number of grade A embryos in group IV (two embryos) did not allow comparison with the other classes. These data do not suggest that PBI selection can contribute to identification of embryos with high developmental ability. In order to establish alternative criteria for oocyte selection, a metaphase II (MII) spindle analysis was also conducted via Polscope. In oocytes of patients of different age, spindle retardance (which reflects the high order and density of microtubules) was compared with parameters of embryo development. In aged patients, a trend was observed between low retardance and poor embryo quality, although in general the association between retardance and oocyte developmental performance did not reach statistical significance.

Pathologic findings in hysteroscopy before in vitro fertilization-embryo transfer (IVF-ET)

Background. The aim of this study was to evaluate hysteroscopy routinely performed prior to in vitro fertilization-embryo transfer (IVF-ET). Methods. We analyzed in a prospective study 300 patients who underwent hysteroscopy before the first IVF-ET cycle. We analyzed then in a retrospective manner 300 patients who did not perform hysteroscopy. Results. One-hundred-and-eighty (60%) hysteroscopies were normal but 120 (40%) revealed an unsuspected intrauterine abnormality. We did not find statistically significant differences between patients with normal or abnormal hysteroscopy in any characteristic. We found a statistically significant difference in pregnancy rate between women who performed hysteroscopy before IVF-ET cycle and in women who did not perform it. Conclusions. Hysteroscopy, as a routine examination, should be performed before the first IVF-ET cycle in all patients.

Gonadotropin-releasing hormone antagonist and metformin for treatment of polycystic ovary syndrome patients undergoing in vitro fertilization–embryo transfer

Aim. The combination of gonadotropin-releasing hormone (GnRH) antagonist and gonadotropin represents a valid alternative to the classical protocol with GnRH agonist for ovulation induction in patients with polycystic ovary syndrome (PCOS). The use of metformin is of benefit to women with PCOS. The aim of the present study was to compare the stimulation characteristics and in vitro fertilization (IVF)–embryo transfer (ET) outcomes of the standard short GnRH antagonist protocol for ovarian stimulation with or without metformin. Materials and methods. We recruited 40 PCOS patients. The population studied was divided into two groups (A and B). Group A was pretreated for 2 months with metformin 1.5 g/day (Glucophage®; Merck Pharm), and then stimulated with recombinant follicle-stimulating hormone (rFSH) 150 UI/day (Gonal F® 75 UI; Serono). GnRH antagonist, cetrorelix acetate 0.25 mg/day (Cetrotide®; Serono), was started when the leading follicle reached 14 mm diameter on ultrasound scan. Group B was treated only with rFSH 150 UI/day and GnRH antagonist 0.25 mg/day when the leading follicle was ≥14 mm in diameter. Results. In group A we found a statistically significant (p < 0.05) decrease in the number of ampoules of rFSH (A vs. B: 18±6 vs. 24±8) and estradiol levels (A vs. B: 2400±600 vs. 3370±900 pg/ml) (all values mean±standard deviation). Group A had significantly fewer cancelled cycles (A vs. B: 1 vs. 3; p < 0.05). The incidence of ovarian hyperstimulation syndrome was 5% in group A and 15% in group B (p < 0.05). In patients treated with metformin, the total number of follicles on the day of human chorionic gonadotropin treatment (23±1.2 vs. 33±2.6) was decreased with no change in the number of follicles ≥14 mm in diameter (A vs. B: 18±1.2 vs. 19±1.7). However, the mean number of mature oocytes (A vs. B: 8.4±1.5 vs. 5.0±1.5) was increased with metformin treatment (p < 0.05). No difference was found in the number of cleaved embryos (A vs. B: 2.5±0.5 vs. 2.2±0.3). Conclusions. The use of metformin with GnRH antagonist improves the outcome of ovarian stimulation in IVF-ET cycles in PCOS patients.

Continuous low‐dose oral contraceptive in the treatment of colorectal endometriosis evaluated by rectal endoscopic ultrasonography

Objective. Limited attention has been focused on the medical treatment of bowel endometriosis. This study evaluates the efficacy of administration of a continuous low‐dose oral contraceptive in treating pain and other symptoms associated with colorectal endometriotic nodules, as evaluated by rectal endoscopic ultrasonography. Design. Prospective observational study. Setting. Academic Department of San Raffaele Scientific Institute, Obstetrics and Gynecology Unit. Population. Symptomatic women of reproductive age (n=26) with colorectal nodules infiltrating at least the bowel muscularis propria and without a stenosis >50%. In 31% of the patients, endoscopic ultrasonography permitted diagnosis of nodules located more than 10 cm from the anal rim. Methods. Patients received a continuous low‐dose oral contraceptive containing 15 μg ethinylestradiol and 60 μg gestodene for 12 months. Subjective symptoms were prospectively evaluated, and nodule volumes were monitored using endoscopic ultrasonography. Main outcome measures. Nodule measurements were performed at baseline and after 12 months of treatment. Symptoms at the start and after 12 months were evaluated. Results. A significant improvement in the intensity of all the considered symptoms (dysmenorrhea, non‐menstrual pelvic pain, deep dyspareunia and painful defecation) was seen when evaluated by a visual analog scale. A reduction in terms of both diameter (mean reduction 26%) and volume of the nodules (mean reduction 62%) was observed after a 12 month period. Conclusions. A continuous low‐dose oral contraceptive therapy may reduce bowel endometriosis‐associated symptoms. In addition, this therapy induces a significant volumetric reduction of colorectal plaques when evaluated by endoscopic ultrasonography.

Natural cycle as first approach in aged patients with elevated follicle-stimulating hormone undergoing intracytoplasmic sperm injection: a pilot study.

Background. Poor ovarian response to standard in vitro fertilization–embryo transfer (IVF-ET) protocols or different regimens of treatment, as consequence of a diminished ovarian reserve, correlates strictly with patient age, elevated follicle-stimulating hormone (FSH) and reduced antral follicle count. The aim of the present pilot study was to evaluate the outcome of patients with poor prognostic features undergoing IVF-ET with natural cycles as a first approach and not as a consequence of a previous failure treatment. Materials and methods. Eighteen aged patients (mean ± standard deviation 40.2 ± 0.7 years, range 37–43 years) with elevated serum FSH and reduced antral follicle count underwent intracytoplasmic sperm injection (ICSI) after spontaneous ovulation. Results. A total of 26 natural cycles with ICSI were analyzed. Pregnancy was observed in three patients, of which two were ongoing as assessed by fetal heart beat at ultrasound scan performed 4–5 weeks after ET. Conclusion. The overall pregnancy rates achieved (11.5% per cycle, 20.0% per ET) are comparable with those of conventional IVF-ET in aged patients, and not impaired by a single embryo transferred. Better embryo quality, as a consequence of natural selection of oocytes, better endometrium receptivity and monthly repeatability of the procedure, can balance the relatively low chance to perform ET.

High Prevalence of Vitamin D Deficiency in Infertile Women Referring for Assisted Reproduction

A comprehensive analysis of the vitamin D status of infertile women is the first step in understanding hypovitaminosis impact on reproductive potential. We sought to determine vitamin D profiles of women attending an infertility center and to investigate non-dietary determinants of vitamin D status in this population. In this cross-sectional analysis, a cohort of 1072 women (mean age ± standard deviation 36.3 ± 4.4 years) attending an academic infertility center was used to examine serum 25-hydroxy-vitamin D (25(OH)D) levels in relation to demographic characteristics, seasons and general health risk factors. Both unadjusted and adjusted levels of serum 25(OH)D were examined. Median 25(OH)D concentration was below 30 ng/mL for 89% of the entire year. Over the whole year, 6.5% of patients had 25(OH)D levels ≤10 ng/mL, 40.1% ≤20 ng/mL, and 77.4% ≤30 ng/mL. Global solar radiation was weakly correlated with 25(OH)D levels. At multivariable analysis, 25(OH)D levels were inversely associated with BMI; conversely, 25(OH)D levels were positively associated with height and endometriosis history. Serum 25(OH)D levels are highly deficient in women seeking medical help for couple’s infertility. Levels are significantly associated with body composition, seasonal modifications and causes of infertility. Importantly, this deficiency status may last during pregnancy with more severe consequences.

Consecutive cycles in in vitro fertilization-embryo transfer

Background. The decline of female fertility with advancing age is well documented. The aim of this study was to compare the ovarian performance after repeated ovarian stimulation cycles in women of different ages. Methods. Four hundred patients who started at least three in vitro fertilization (IVF) cycles during the 5-year period between 1998 and 2002 were identified. The patients were divided into four groups: the 25–30 age group (n = 90), the 31–35 age group (n = 150), the 36–40 age group (n = 110) and the 41–45 age group (n = 50). Results. Comparing subsequent cycles versus the first treatment cycle we found a statistically significantly increased number of ampules of recombinant follicle stimulating hormone (rFSH) needed to reach follicles maturation (p < 0.001). The number of ampules of gonadotropin required was significantly higher (p < 0.001) in the groups of advanced age compared with the groups of young women. For women in the 36–40 group and in the 41–45 group we found the number of follicles, the number of oocytes and the proportion of grade A embryos, in every cycle, were significantly lower than in the groups of young women. We compared the characteristics of ovarian stimulation and response of a single age group in different consecutive cycles. We found significant differences (p < 0.05) only in the number of ampules required. Conclusions. Maternal age adversely affected ovarian performance. During repeated IVF cycles we also noted an age-independent decline of ovarian response.

Laparoscopic treatment of deep pelvic endometriosis with rectal involvement.

PURPOSE: Our study aimed to evaluate the feasibility and outcome of laparoscopic excision of deep pelvic endometriosis with extensive rectal involvement causing severe symptoms. METHODS: Ten patients, mean age 32 years (range, 27-43), with deep pelvic endometriosis and rectal wall involvement, requiring surgical resection, were studied since January 2004. Prior to surgery and 6 months postsurgery, patients completed a 100-point rank questionnaire on intensity of intestinal and extraintestinal symptoms. A laparoscopic approach was performed by a team of a gynecologist and colorectal surgeons. RESULTS: At surgery, complete excision of infiltrating endometriosis was achieved, with 7 low rectal resections, 2 rectosigmoid resections, and 1 proctectomy with coloanal anastomosis. Additional procedures were: ureter resections (n = 2) with one reimplantation in the bladder, left ovariectomies (n = 2), ovarian endometrioma resections (n = 4), and laser ablation of superficial peritoneal lesions (n = 4). In four cases, a laparotomic conversion was needed. Mean follow-up was 27.6 months (range, 18-37). Neither intraoperative nor postoperative serious complications were observed. All the patients experienced significant improvement of intestinal and extraintestinal symptoms. CONCLUSIONS: Laparoscopic resection of deep pelvic endometriosis with rectal involvement can be successful in improving digestive and gynecologic symptoms; however, this approach is challenging with a high rate of laparotomic conversion.