Emerging gonadotropin-releasing hormone agonists.

INTRODUCTION: Gonadotropin-releasing hormone agonist analogs (GnRHa) are peptides that mimic the action of gonadotropin-releasing hormone (GnRH) and are used to suppress subsequent sex steroid production. Although the analogs are a rather defined group of drugs, there have been developments in the past decades and there is still ample room for improvement. New therapeutic strategies in the use of GnRHs are discussed. AREAS COVERED: Major points of discussion include: i) the use of concomitant treatment of early breast cancer in premenopausal estrogen-positive and -negative patients, ii) the use of GnRHa for fertility preservation in young female patients with malignant diseases and iii) the use of GnRH analogs in assisted reproduction. The manuscript provides a better understanding of GnRH agonists as well as an explanation of their major indications, biochemical pathways and concluding therapeutic strategies. Recent results from international meetings and debates are described to explain current controversies. EXPERT OPINION: This paper highlights the need for more complex GnRH analogs. In the next few years, there will be longer acting GnRHas that may improve adherence. New therapeutic targets in oncological concepts may go beyond fertility preservation and focus on the antiproliferative effects of GnRH analogs.

Teenage deliveries in Northern Germany: always a risk factor for higher surgical delivery rates?

PURPOSE: To evaluate the impact of young maternal age on labour, intrapartum assessment and delivery mode. METHODS: A retrospective cohort analysis was conducted of 13,941 deliveries at a tertiary delivery unit between 2000 and 2009. Patients aged less than 18 years were compared with patients aged 18 years or older. The main outcome was defined as mode of delivery. Frequencies and odds ratios for adverse maternal-foetal outcomes were calculated for primiparous women. RESULTS: Of the deliveries occurring during the study period, 6,863 (49.2%) met the inclusion criteria. A total of 156 deliveries (2.3%) occurred among teenagers less than 18 years and 6,707 among patients 18 years and older. Compared with patients 18 years of age and older, younger maternal age was associated with a higher chance of spontaneous delivery [adjusted odds ratio (OR) 2.07, 95% confidence interval (CI) 1.45-2.93] than via operation (vaginal operative delivery: OR 0.98, 95% CI 0.48-2.03; secondary caesarean delivery: adjusted OR 0.51, 95% CI 0.32-0.82). CONCLUSION: Young maternal age at delivery does not represent a risk factor for high surgical delivery rates.

Obesity decreases the chance to deliver spontaneously.

PURPOSE: To evaluate the impact of maternal obesity on labour, intrapartual assessment and delivery. METHODS: Retrospective cohort analysis of n = 11,681 deliveries supervised between 01 January 2000 and 31 December 2009. Results were analysed dividing the patients into two main groups according to their body mass index (BMI): group 1, control: BMI 18-24.9 and group 2 BMI, test >25. Subgroups were built: (0) BMI 25-29.9, (I) BMI 30-34.9, (II) BMI 35-39.9, (III) BMI >40. Exclusion criteria were defined as: delivery <37 + 0 weeks p.m., multiple pregnancy, comorbidity other than GDM, abnormal presentation, BMI <18.5, and incomplete data. The main outcome parameter was defined as secondary caesarean delivery rate and mode of delivery. RESULTS: N = 8,379 patients met the inclusion criteria and were divided in two groups: 1, n = 4,464 patients and 2, n = 3,915. Basic maternal characteristics including foetal vital parameters were equal in all groups. GDM occurred more frequently in obese patients (P < 0.001). For the main outcome parameter a significant decrease in the rate of spontaneous delivery between control/test groups (72-66%, P < 0.001) and control/I-III groups (72 vs. 50%, P < 0.001) could be observed. The rate of secondary c-section increased significantly according to a higher BMI (>40: OR 2.5, 95% CI 1.84-3.61, χ (2) P < 0.001). The groups showed no difference in the rate of injuries during delivery though foetal birth weight increased significantly with a higher BMI (3,412-3,681 g; P < 0.001). CONCLUSION: Obesity decreases the chance to deliver spontaneously. Moreover, the obese patient suffers from a significantly longer trial of labour (7.9 vs. 9.5 h) and an elevated risk of surgical delivery.

Prenatal course and outcome in 103 cases of fetal spina bifida: a single center experience.

OBJECTIVE: To investigate the prenatal course and functional outcome for fetuses with spina bifida according to the level of the spinal lesion at prenatal ultrasound examination. DESIGN: Retrospective, descriptive study. SETTING: Tertiary referral center, Germany. POPULATION: A total of 103 fetuses with spina bifida identified between 1993 and 2008. METHODS: The antenatal course and postnatal outcome for affected fetuses were reviewed. The relation of relevant outcome domains to the anatomical level was assessed using Fisher's exact test and the χ(2)-test. MAIN OUTCOME MEASURES: Level and type of spinal lesion, pregnancy outcome, psychomotor development, bladder and bowel function. RESULTS: Our cohort included a total of 31 live born infants, 68 terminated pregnancies, four intrauterine fetal deaths and five postnatal deaths. Four cases were excluded from follow-up. Twenty of the remaining 22 infants had normal or only slightly impaired mental development (91%). Thirteen children (59%) were able to walk, but nine (41%) needed wheelchairs or were paraplegic. The rate of poor motor outcome varied strongly in dependence on the level of the lesion (22.2% at lower lumbosacral levels to 80% at thoracic level). The majority of the affected children (16/22, 72.7%) suffered from impairment of bladder function. In 36% of cases (8/22) anal incontinence was documented. CONCLUSION: Spina bifida can result in a spectrum of disabilities that frequently lead to an impairment of bladder, bowel and motor function. The motor function depended on level of the lesion.

Vitrified-warmed embryo transfer is associated with mean higher singleton birth weight compared to fresh embryo transfer.

OBJECTIVE: To test for differences in birth weight between singletons born after IVF with fresh embryo transfer vs. vitrified-warmed 2PN embryo transfer (vitrification protocol). DESIGN: Retrospective analysis of 464 singleton live births after IVF or ICSI during a 12 year period. SETTING: University hospital. INTERVENTIONS: Fresh embryo transfer, vitrified-warmed 2PN embryo transfer (vitrification protocol). MAIN OUTCOME MEASURES: Birth weight standardized as a z-score, adjusting for gestational week at delivery and fetal sex. As a reference, birth weight means from regular deliveries from the same hospital were used. Multivariate regression analysis was used to investigate the relationship between the dependent variable z-score (fetal birth weight) and the independent predictor variables maternal age, weight, height, body mass index, RDS prophylaxis, transfer protocol, number of embryos transferred, indication for IVF treatment and sperm quality. RESULTS: The mean z-score was significantly lower after fresh transfer (-0.11±92) as compared to vitrification transfer (0.72±83) (p<0.001). Multivariate regression analysis indicated that only maternal height and maternal body mass index, but not type of cryopreservation protocol, was a significant predictor of birth weight. CONCLUSIONS: In this analysis focusing on 2PN oocytes, vitrified-warmed embryo transfer is associated with mean higher birth weight compared to fresh embryo transfer. Maternal height and body mass index are significant confounders of fetal birth weight and need to be taken into account when studying birth weight differences between ART protocols.

Cornelia de Lange syndrome: antenatal diagnosis in two consecutive pregnancies due to rare gonadal mosaicism of NIPBL gene mutation.

Cornelia de Lange syndrome (CdLS) (also referred to as Brachmann-de Lange syndrome) constitutes a multisystem developmental anomaly which is characterized by facial dysmorphism, upper limb deformities, and mental retardation. We report on two subsequent pregnancies with antenatally diagnosed CdLS at 23 and 14 gestational weeks, respectively, of an otherwise healthy gravida. Molecular genetic testing revealed a rare case of gonadal mosaicism of a nonsense NIPBL gene mutation.