Simone Giulini

Anti-Mullerian Hormone in Premenopausal Women and After Spontaneous or Surgically Induced Menopause

Objective: The objectives of this study were: (1) to determine anti-Mullerian hormone (AMH) levels in menopausal women, and (2) to confirm the source of AMH in cycling women and its disapperance after the removal of the source. Methods: An observational and prospective study was conducted. Results: A total of 47 women were recruited for the study. The study population consisted of the following groups of patients: (A) women of late reproductive age (n= 24; mean age ± SD, 44 ± 2.8 years); (B) menopausal women (n= 14; mean age, 56 ± 4 years); (C) regularly cycling women undergoing surgical menopause (n= 9; mean age, 43 ± 4 years). Blood samples were obtained from all patients. In patients undergoing surgery, blood samples were obtained before and after surgery. AMH was undetectable in 13 of 14 postmenopausal women, whereas it was undetectacle in only two of 24 women of late reproductive age. A significant negative correlation has been found between AMH and age or follicle-stimulating hormone (FSH) in women of late reproductive age. In women who were candidates for oophorectomy, samples were obtained 3-5 days after surgery. AMH was undetectable after the surgery in all women. Conclusions: We found that AMH levels decreased in women in the late reproductive period and that menopause and ovariectomy in regularly cycling women are associated to undetectable AMH in serum. These observations confirm that the ovary could be the only source of AMH in women and that it is a novel marker for ovarian aging.

Age-specific nomogram for the decline in antral follicle count throughout the reproductive period

OBJECTIVE To investigate the relationship between antral follicle count (AFC) and chronological age and to establish normal values for AFC in women with regular menstrual cycles. DESIGN Cross-sectional study. SETTING University hospital. PATIENT(S) Four hundred fifteen premenopausal women were recruited for the study. Data from 362 patients were available for the statistical analysis. INTERVENTION(S) AFC was measured by transvaginal ultrasound examination. MAIN OUTCOME MEASURE(S) Estimating the relationship between AFC and age and developing the AFC nomogram. RESULT(S) The analysis showed a linear decline in AFC with age; for every year increase in age, the median AFC decreases by 0.4. The AFC corresponding to the 5th, 25th, 50th, 75th, and 95th centiles for each age have been calculated. CONCLUSION(S) A linear relationship of AFC to age was found. For the first time, a nomogram reporting normal and interquartile values for AFC, age by age, throughout the reproductive period has been provided. Until now, the interpretation of the measurement was mainly based on the individual experience of the operator, because no normative data were present. Therefore, the establishment of a nomogram of AFC values is the first step to counsel patients on a scientific basis.

Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle‐stimulating hormone starting dose in in vitro fertilisation cycles

Please cite this paper as: La Marca A, Papaleo E, Grisendi V, Argento C, Giulini S, Volpe A. Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle‐stimulating hormone starting dose in in vitro fertilisation cycles. BJOG 2012;119:1171–1179.

Doppler, ultrasonographic and endocrinological environment with regard to the number of small subcapsular follicles in polycystic ovary syndrome

The aim of this study was to evaluate how, in patients with polycystic ovary syndrome, the number of small subcapsular follicles correlates with uterine and ovarian blood flow and with specific hormonal parameters. At an ultrasonographic evaluation, 30 patients with polycystic ovary syndrome showed 5-10 (group I; n = 14) or > 10 (group II; n = 16) small follicles. These patients underwent ultrasonographic (ovarian volume and stroma echodensity; number, diameter and distribution of follicles) and color Doppler (uterine and intraovarian vessels) analyses, and hormonal assay. In group II, significantly lower pulsatility index values than in group I were observed in the ovarian stromal arteries. The Ferriman-Gallwey score, plasma androstenedione level and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio results were significantly higher in group II than in group I. Androstenedione plasma levels correlated with the number of small follicles. Furthermore, the LH/FSH ratio correlated with both the number of small follicles and the stromal artery pulsatility index. The combined assessment of ovarian morphology by transvaginal ultrasound and color Doppler may provide insight into the pathological state of polycystic ovary syndrome.

Embryo quality and implantation rate in two different culture media: ISM1 versus Universal IVF Medium

OBJECTIVE To compare the outcome of two different culture media marketed by the MediCult AS Company (Jyllinge, Denmark)-Universal IVF Medium and ISM1 Medium culture-which, in addition to glucose, pyruvate, and energy-providing components, also contain amino acids, nucleotides, vitamins, and cholesterol. DESIGN Laboratory and retrospective clinical study. SETTING University teaching hospital. PATIENT(S) A total of 726 patients, undergoing IVF-intracytoplasmic sperm injection procedure, comparable in mean age range, oocyte retrieval, and infertility indication, were included in the study. Laboratory quality and standard procedures were maintained unaffected. INTERVENTION(S) Oocyte retrieval, different embryo culture media. MAIN OUTCOME MEASURE(S) Embryo quality, ongoing pregnancy, and implantation rate. RESULT(S) The frequency of good-quality embryos (79% vs. 74%) and the percentages of ongoing pregnancy (27.5% vs. 18%) and implantation rate (15% vs. 10%) were significantly higher in the group treated with ISM1 Medium rather than Universal IVF Medium. CONCLUSION(S) ISM1 Medium culture seems to improve the performance of embryonic growth and development, as well as increasing the percentage of pregnancy.

Short Communication: Severe Intraabdominal Bleeding After Transvaginal Oocyte Retrieval for IVF-ET and Coagulation Factor XI Deficiency: A Case Report

Assisted reproductive techniques have become well-accepted methods for the treatment of infertile couples. Although they are practiced widely almost everywhere in the world, a debate regarding their efficacy, cost/effectiveness, risk factors, and side effects still exists. Ultrasonographic guided vaginal oocyte recovery is a relatively atraumatic method with rare complications. Since Wickland (1) first described the technique, it was rapidly accepted and spread becoming the method of choice in most IVF programs. Transvaginal ovum pick-up has proven to be efficient (high recovery rate of good quality oocytes) with minimal discomfort for patients in large reported IVF series. Furthermore, this procedure allows the use of local anesthesia with sedation, is rapid and easy to perform, decreases the cost to the patient, and permits a quick postoperative recovery. Nevertheless, despite the advantages, the aspiration needle may injure the adjacent pelvic organs and structures inducing serious, and sometimes even fatal, complications: vaginal wall hemorrhage (2), hemoperitoneum because of ovarian or pelvic blood vessel lesions (3–5), infection or exacerbation of pelvic inflammatory diseases (6), rupture of endometriotic cystic masses, urinary tract infections, or ureteral lesions (7). The case we present here describes a hemoperitoneum in which, at laparotomy, it was not possible to observe a direct damage of any blood vessel. However, retrospectively, a deficit of coagulation factor XI was shown.

Color Doppler analysis in oligo-and amenorrheic women with polycystic ovary syndrome

The objective of this study was to determine whether amenorrheic women have more severe blood flow variations and clinical-endocrinological patterns in comparison with oligomenorrheic polycystic ovary syndrome (PCOS) patients. Twenty oligomenorrheic women (cycle length > 35 days; Group I), and 20 amenorrheic women (no vaginal bleeding for at least 6 months; Group II) were submitted to ultrasonographic evaluation of ovarian volume, follicle distribution, number and diameter, color Doppler analysis of uterine and intraovarian blood flow, hormonal assay of different compartments, and plasma evaluation of lipid profile. The number of subcapsular small-sized follicles, and the ovarian volume, androstenedione and luteinizing hormone (LH) plasma levels, and the LH/follicle-stimulating hormone (FSH) ratio were significantly higher in the amenorrheic group compared with the oligomenorrheic patients. Furthermore, significantly lower high-density lipoprotein (HDL) and HDL/total cholesterol ratio were observed in Group II compared with Group I. In addition, in Group II, higher resistance in the uterine arteries and lower impedance to blood flow in the intraovarian arteries have been shown. The assessment of ovarian morphology by transvaginal ultrasound and Doppler flow analysis of both intraovarian and uterine arteries in patients with PCOS may provide an insight into the pathological state and the degree of progression of the disease.

Individualization of the FSH starting dose in IVF/ICSI cycles using the antral follicle count

BackgroundThe FSH starting dose is usually chosen according to women’s age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC), which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles.MethodsThis is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505) were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model.ResultsA model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively.ConclusionsThe daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice.

Human ovarian tissue cryopreservation: effect of sucrose concentration on morphological features after thawing

Recent improvements in techniques in clinical assisted reproduction have led to an increased interest in the cryopreservation of human ovarian tissue as a way of preserving fertility and ovarian steroidogenic activity in young cancer patients. Acceptable follicular survival in frozen-thawed human ovarian tissue has generally been reported. Since a 0.3 mol/l sucrose concentration in cryopreservation solutions evidently increases human oocyte survival after cryopreservation, the aim of this study was to observe the effect of sucrose concentrations of 0.2 mol/l and 0.3 mol/l on human ovarian tissue survival after thawing. Ovarian cortical slices from 10 patients, 22-36 years of age, were cryopreserved slowly using 0.2 mol/l or 0.3 mol/l sucrose with 1,2-propanediol (1.5 mol/l) as the cryoprotectants. Light and electron microscopy were used for the histological analyses. Results showed that both treatments produced an increase in damaged cells; however, the use of 0.3 mol/l sucrose showed a smaller percentage of damaged germ cells than 0.2 mol/l sucrose, and therefore was less detrimental to the thawed ovarian tissue. However as the damage occurred principally in the stroma and follicular cells rather than in the oocytes, the suitability of these cryopreservation protocols must be further evaluated prior to considering the use of stored ovarian cortex for autografting after thawing.

Intratesticular Doppler flow, seminal plasma nitrites/nitrates, and nonobstructive sperm extraction from patients with obstructive and nonobstructive azoospermia.

OBJECTIVE To prospectively evaluate the role of intratesticular vascular flow in modulating sperm function in men with obstructive and nonobstructive azoospermia. The correlation of testicular Doppler values with nitric oxide and testicular sperm extraction was further evaluated. DESIGN Prospective study. SETTING Assisted reproduction unit at a university center. PATIENT(S) Twenty-eight men with azoospermia undergoing sperm extraction for intracytoplasmic sperm injection. INTERVENTION(S) Ultrasound and color Doppler scanning of the testes. Testicular sperm retrieval and nitrite/nitrate assay. MAIN OUTCOME MEASURE(S) Doppler analysis of testicular transmediastinal artery, plasma and seminal plasma nitrite/nitrate values, and sperm extraction histopathology. RESULT(S) The pulsatility index (PI) of the transmediastinal artery was higher in patients with nonobstructive azoospermia (PI = 1.40 +/- 0.13) than in those with obstructive azoospermia (PI = 1.09 +/- 0.15; P=.011). Seminal plasma nitrite/nitrate concentrations were more elevated in cases of obstructive azoospermia than in gonadal failure. Unsuccessful sperm recovery was observed in four patients who showed the worst indices of gonadal failure. In this subgroup, a transmediastinal PI value >1.50 was always observed. CONCLUSION(S) Doppler analysis of the transmediastinal artery and nitrite/nitrate seminal plasma concentrations are useful for distinguishing between obstructive and nonobstructive azoospermia and allow the identification of the presence of spermatozoa within the testes.