G. De Placido

Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism

The aim of this observational preliminary trial was to estimate the association between the most common polymorphism of LH (LH-β variant: v-βLH), with different profiles of ovarian response to recombinant human FSH (rhFSH). A total of 60 normogonadotrophic patients undergoing a gonadotrophin-releasing hormone analogue long down-regulation protocol followed by stimulation with recombinant human FSH (rhFSH) for IVF/intracytoplasmic sperm injection, and in whom at least five oocytes were retrieved were retrospectively included. On the basis of the total rhFSH consumption, patients were divided into three groups: Group A: 22 women requiring a cumulative dose of rhFSH >3500 IU; Group B: 15 patients requiring 2000-3500 IU; Group C (control): 23 women requiring <2000 IU. The presence of v-βLH was evaluated using specific immunoassays. Peak oestradiol concentrations were significantly lower in Group A when compared with both groups B (P < 0.05) and C (P < 0.001). Group A had a significantly lower (P < 0.05) number of oocytes retrieved (7.3 ± 1.5, 11.7 ± 2.4 and 14.7 ± 4.1 in the three groups, respectively). Seven carriers (31.8%) of v-βLH were found in Group A, whereas only one variant (6.7%) was observed in Group B; no variant was detected in Group C. These preliminary results suggest that v-βLH is more frequent in women with ovarian resistance to rhFSH.

Intra-follicular leptin concentration as a predictive factor for in vitro oocyte fertilization in assisted reproductive techniques

Background: Granulosa-cells are able to produce and store leptin, suggesting that this hormone is locally involved in the regulation of follicular growth. In this study, the role of follicular fluid (FF) leptin concentration in predicting oocyte fertilization and embryo quality was evaluated in 35 normogonadotrophic women undergoing controlled ovarian stimulation (COS) for assisted reproductive techniques. Materials and Methods: Leptin concentration was measured in 47 consecutively collected FF in which a mature oocyte had been found during the ovum pick-up. Embryos deriving from fertilized oocytes were submitted to quality scoring systems. Results: Mean leptin concentration was significantly higher in FF whose oocytes showed 2 pronuclei (no. 25) when compared with those with no evidence of fertilization (no. 22) at the 16–18 h check (26.0±6.1 vs 15.3±10.6 ng/ml, respectively, p<0.01). Follicular mean diameters were similar in the two groups (21.4±3.4 and 21.0±5.1 mm, respectively). Logistic regression analysis identified FF leptin levels as the best predictive parameter for oocyte fertilization (p<0.001). When receiving operating characteristics curve was employed, a FF leptin concentration of 20.25 ng/ml was the most reliable cut-off in predicting fertilization of oocytes. FF with leptin concentrations higher than this value (no. 27) had an oocyte fertilization rate of 85.7%. In contrast, FF levels ≤20.25 ng/ml (no. 20) were associated with a rate of 16.7% (p<0.05). No correlation emerged between FF leptin and the score attributed to 15 valuable embryos at the zygote stage (r=−0.01) and at 48 h after insemination (r=0.1). Conclusions: FF leptin levels are a better predictor of oocyte fertilization success rates than follicular diameter. These results underline the relevance of FF variables in developing methods for oocyte selection.

The combination of genetic variants of the FSHB and FSHR genes affects serum FSH in women of reproductive age

STUDY QUESTION What is the effect of FSHB-211G>T together with the FSHR 2039 A>G on serum FSH in women? SUMMARY ANSWER Serum FSH levels are affected by the combination of genetic polymorphisms in FSHR and FSHB. WHAT IS KNOWN ALREADY The relationship between SNPs of the FSHR gene and serum FSH has not been completely clarified. Genetic variants of the FSHB gene have been associated with variation in gene transcription and serum FSH levels in men. No data have been published on the effect of the FSHB-211G>T in women, alone or in combination with the FSHR 2039 A>G. STUDY DESIGN, SIZE, DURATION This study was a prospective study including 193 healthy women of reproductive age. PARTICIPANTS/MATERIALS, SETTING, METHODS Infertile and otherwise healthy eumenorrheic women (n = 193) with normal BMI and serum FSH levels were recruited for the study. In all women early follicular phase FSH and AMH were measured by commercial assays, and antral follicle count was measured by transvaginal ultrasound. Genomic DNA was purified from total peripheral blood and genotyping for the two SNPs was performed. MAIN RESULTS AND THE ROLE OF CHANCE No significant gradients of increasing or decreasing Day 3 FSH across the FSHR 2039 (AA/AG/GG) and FSHB-211 (GG/GT/TT) genotypes, respectively, were observed. When women were stratified according to the FSHR 2039, and FSHB-211 genotypes a statistically significant reduction of d3 FSH was shown in the group of women with the FSHB-211 GT + TT/FSHR2039 AA genotype compared with the FSHB-211 GG/FSHR2039 GG genotype, hence confirming a possible additive effect of the different SNPs in FSHR and FSHB on regulating serum FSH. LIMITATIONS, REASONS FOR CAUTION This finding requires an independent confirmation. However, it confirms the relationship between serum FSH and FSHB together with FSHR gene polymorphisms already reported in males. WIDER IMPLICATIONS OF THE FINDINGS The knowledge of the FSHB/FSHR genotype combination is fundamental for the proper interpretation of serum FSH levels in women of reproductive age. STUDY FUNDING/COMPETING INTERESTS Merck Serono supported the study in the form of a research grant for the laboratory session. None of the authors have any competing interest to declare.

Association of pelvic endometriosis with alopecia universalis, autoimmune thyroiditis and multiple sclerosis.

An adult Caucasian female developed a previously unreported association of pelvic endometriosis (PE) with the triad of alopecia universalis (AU), autoimmune thyroiditis (AT) and multiple sclerosis (MS). Molecular human leukocyte antigen (HLA)-tissue typing of this subject showed the presence of the DR(2) 15 and DR(3) 17 alleles, which are associated to an increased risk of MS and AT, respectively. Clinical onset of AT followed withdrawal of corticosteroid treatment for AU, whereas MS become clinically evident after withdrawal from long-term estroprogestin therapy for PE. This clinical case is presented to discuss the autoimmune origin of PE, its possible association with multiple autoimmune disorders as well as the effect of other factors, such as administration and/or discontinuation of specific hormonal regimens, on genetic autoimmunity-prone background.

Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation

BackgroundGonadotropins are protein hormones which are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. There is still a lively debate on which type of gonadotropin medication should be used, either human menopausal gonadotropin or recombinant follicle-stimulating hormone. The objective of the study was to perform a systematic review of the recent literature to compare recombinant follicle-stimulating hormone to human menopausal gonadotropin with the aim to assess any differences in terms of efficacy and to provide a cost evaluation based on findings of this systematic review.MethodsThe review was conducted selecting prospective, randomized, controlled trials comparing the two gonadotropin medications from a literature search of several databases. The outcome measure used to evaluate efficacy was the number of oocytes retrieved per cycle. In addition, a cost evaluation was performed based on retrieved efficacy data.ResultsThe number of oocytes retrieved appeared to be higher for human menopausal gonadotropin in only 2 studies while 10 out of 13 studies showed a higher mean number of oocytes retrieved per cycle for recombinant follicle-stimulating hormone. The results of the cost evaluation provided a similar cost per oocyte for both hormones.ConclusionsRecombinant follicle-stimulating hormone treatment resulted in a higher oocytes yield per cycle than human menopausal gonadotropin at similar cost per oocyte.

Vaginal lactoferrin in asymptomatic patients at low risk for pre-term labour for shortened cervix: Cervical length and interleukin-6 changes

A total of 3,324 singleton pregnant women were screened for pre-term delivery and 128 women were finally randomised and analysed for outcome showing borderline cervical length (25–29 mm) and elevated cervico-vaginal interleukin 6 levels. To verify if vaginal administration of lactoferrin might have an influence on these variables, two groups of 64 patients were formed. Study cases were submitted to lactoferrin for 21 days; controls received no treatment. An inverse relation was found between interleukin 6 levels and cervical length. On day 30 from the beginning of the treatment, study cases showed a decrease in interleukin 6 levels and an increase in cervical length. A greater number of women with regular uterine contractions and reduced cervical consistency before the 37th week of gestation were found in the controls. Our data show that lactoferrin could play a role in reducing the number of women at risk for pre-term birth for shortened cervical length and elevated interleukin 6 levels.

A prospective, randomised, investigator-blind, controlled, clinical study on the clinical efficacy and tolerability of two highly purified hMG preparations administered subcutaneously in women undergoing IVF

Abstract The aim of this multicentre, prospective, randomised, investigator blind, controlled clinical trial was to evaluate the clinical efficacy and tolerability of a highly purified human menopausal gonadotrophin (hMG) preparation (Merional-HG) when administered to patients undergoing controlled ovarian stimulation (COS) for in-vitro fertilisation (IVF) procedure enrolled in hospital departments. One hundred fifty-seven patients were randomised in two parallel groups: 78 started COS with Merional-HG and 79 with Menopur. Results of the study showed that both highly purified hMG preparations were equivalent in terms of number of oocytes retrieved (primary endpoint: 8.8 ± 3.9 versus 8.4 ± 3.8, p = 0.54). In the patients treated with Merional-HG, we observed a higher occurrence of mature oocytes (78.3% versus 71.4%, p = 0.005) and a reduced quantity of gonadotrophins administered per cycle (2.556 ± 636 IU versus 2.969 ± 855 IU, p < 0.001). Fertilisation, cleavage, implantation rates and the number of positive β-human chorionic gonadotrophin (hCG; pregnancy) tests and the clinical pregnancy rate were comparable in the two groups. Both treatments were well tolerated. In conclusion, the results of this study support the efficacy and safety of Merional-HG administered subcutaneously for assisted reproduction techniques. Efficiency of Merional-HG appears to be higher due to reduced quantity of drug used and the higher yield of mature oocytes retrieved.

O43 A common LH polymorphism is associated with higher FSH consumption during ovarian stimulation for IVF/ICSI cycles

Material and Methods: This is a retrospective study of patients delivered in the maternity department in TMC over 12 years from 1996 to 2008. Information was taken from the delivery suit registration book and department registration files. Results: The number of HIV infected mothers giving birth in Tripoli Medical Centre is steadily increasing since the hospital opened in September 1996. In 1997 HIV infected mothers constituted 2.5/10 000 of deliveries, this increased to 40/10 000 deliveries in 2008, which is higher than incidence of HIV in Tripoli (0.3%), Overall we have 221 cases of HIV infected mothers giving birth in TMC, /4 of these were in the last 4 years. We only have details on 150 of these patients. We are aware of only one mortality in these patients. Age of patients ranged from 17 to 43 and their nationality varied from 100% non Libyan (mainly African origin) in 1996 up to nearly 96% Libyan in the last couple of years. Regarding the mode of delivery all patients were delivered normally between 1996–2002, since then more patients are being delivered by elective cesarean section. Babies of HIV mothers have a higher rate of being still birth or admitted to neonatal intensive care than the average hospital rate. Conclusion:With the increasing incidence of HIV among our Libyan mothers, doctors and midwifes need to be trained in dealing with these patients with the aim to reduce neonatal infection.

Influence of cryopreservation on perinatal outcome after blastocyst- vs cleavage-stage embryo transfer: systematic review and meta-analysis

To compare the perinatal outcomes of singleton pregnancies resulting from blastocyst‐ vs cleavage‐stage embryo transfer and to assess whether they differ between fresh and frozen embryo transfer cycles.

P14.07: Fetal akinesia deformation sequence associated with cystic hygroma colli in a fetus affected by Down syndrome, at 11–14 weeks' gestation

Objective: To assess the pregnancy outcome and neonatal follow-up in fetuses with first trimester increased nuchal translucency (> p97.5) and normal karyotype. Methods: For an optimal follow-up, a specific clinic attended by an obstetrician has been established since October 2002. Fetal echocardiography (14 and 20 weeks), early anomaly scan (12–14 w), anomaly scan at 20 weeks with nuchal fold measurement and maternal infection screening (CMV, toxoplasmosis and parvovirus B19) have been allocated. Newborn follow-up has been established during the first year of life. Results: From October 2002 to February 2004, 52 fetuses with increased NT and normal karyotype were detected. A structural defect or genetic syndrome was diagnosed in 14 cases (26%): 6 cardiac defects, 2 urinary tract abnormalities, 2 fetal akinesia deformations, 2 fetal hydrops, one multiple malformation and one unespecified syndrome. From these, there was one spontaneous fetal loss at 15 weeks, 7 terminations of pregnancy (TOP), 2 neonatal or infant demises, and the four survivors required medical or surgical treatment. In addition, there was one spontaneous miscarriage at 13 weeks, and one TOP undertaken at 20 weeks, because of PROM with severe oligohydramnios after CVS. Twenty-five newborn (47%) were delivered with no defect and showed normal neurodevelopment up to the first year of life. In all of them, nuchal fold had been resolved by 20 weeks. Finally, there are 9 ongoing pregnancies (17%) with no abnormalities detected in the first half of the pregnancy. Conclusions: Increased NT with normal karyotype is associated with a high incidence of fetal abnormalities (25%). When no anomalies are detected and nuchal fold is normal at 20 weeks, the risk of and adverse outcome is very low.