Metabolism and karyotype analysis of oocytes from patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances which include impaired insulin signalling and glucose metabolism in ovarian follicles. The oocyte is metabolically dependent upon its follicle environment during development, but it is unclear whether PCOS or polycystic ovarian (PCO) morphology alone affect oocyte metabolism and energy-demanding processes such as meiosis. METHODS: Immature human oocytes were donated by PCOS (n = 14), PCO (n = 14) and control (n = 46) patients attending the assisted conception programme at Leeds Teaching Hospitals NHS Trust. Oocytes were cultured individually and carbohydrate metabolism was assessed during overnight in vitro maturation (IVM). Meiotic status was assessed and oocyte intracellular nicotinamide adenine dinucleotide phosphate (NAD(P)H) content and mitochondria activity were measured prior to karyotype analysis by multifluor in situ hybridization. RESULTS: Patient aetiology had no significant effect on oocyte maturation potential or incidence of numerical chromosome abnormalities (44%), although PCOS and PCO oocytes were more likely to suffer predivision. Group G chromosomes were most likely to be involved in non-disjunction and predivision. PCOS was associated with increased glucose consumption (2.06 +/- 0.43 and 0.54 +/- 0.12 pmol/h for PCOS and control oocytes, respectively) and increased pyruvate consumption (18.4 +/- 1.2 and 13.9 +/- 0.9 pmol/h for PCOS and control oocytes, respectively) during IVM. Prior prescription of metformin significantly attenuated pyruvate consumption by maturing oocytes (8.5 +/- 1.8 pmol/h) from PCOS patients. Oocytes from PCO patients had intermediate metabolism profiles. Higher pyruvate turnover was associated with abnormal oocyte karyotypes (13.4 +/- 1.9 and 19.9 +/- 2.1 pmol/h for normal versus abnormal oocytes, respectively). Similarly, oocyte NAD(P)H content was 1.35-fold higher in abnormal oocytes. CONCLUSIONS: The chromosomal constitution of in vitro matured oocytes from PCOS is similar to that of controls, but aspects of oocyte metabolism are perturbed by PCOS. Elevated pyruvate consumption was associated with abnormal oocyte karyotype.

A Case of Live Birth after Uterine Reconstruction for Recurrent Cornual Ectopic Pregnancy following IVF Treatment.

We present a case of recurrent ruptured right cornual ectopic pregnancies conceived after IVF. Following the second episode, a sonohysterography was undertaken to identify possible areas of scar weakness that may rupture with uterine distension in a future pregnancy. The scan revealed asymmetrical muscle thickness in the cornual regions, the right (6 mm) being thinner than the left (1.6 cm). Subsequently, an elective laparotomy was undertaken, and the cornua were reconstructed and thickened in several layers by bringing the laterally retracted myometrial fibres onto the reconstruction site. A sono-hysterography after surgery showed satisfactory (3-4 cm) myometrial thickness all around. A further cycle of IVF resulted in a singleton pregnancy. Pelvic scans confirmed normal intrauterine pregnancy without any myometrial thinning. She was delivered by an uneventful elective caesarean section at term. We propose that, in those who intend to have further pregnancies after a cornual ectopic pregnancy, a sono-hysterography is possibly the best investigative tool to assess myometrial integrity. This case demonstrates that in women with areas of muscle weakness it is possible to successfully perform an interval elective reconstructive surgery on the uterus that can result in an uneventful pregnancy and birth.

Full investigation of patients with polycystic ovary syndrome (PCOS) presenting to four different clinical specialties reveals significant differences and undiagnosed morbidity.

OBJECTIVE: This study aimed to compare the spectrum of polycystic ovary syndrome (PCOS) symptoms in patients from four different specialist clinics. DESIGN: A prospective cross-sectional observational study. SETTING: The study was conducted at the infertility, gynaecology, endocrine and dermatology clinics at Leeds General Infirmary, U.K. PATIENTS: Seventy women presenting with features of PCOS: 20 from infertility, 17 from gynaecology, 17 from dermatology and 16 from endocrine clinics. INTERVENTIONS: Participants were assessed for symptoms and signs of PCOS and underwent a full endocrine and metabolic profile and a pelvic ultrasound scan. RESULTS: All subjects had experienced menstrual problems, 81% were overweight, 86% had polycystic ovaries on ultrasound, 56% had hirsutism, 53% had acne, 23% had acanthosis nigricans, 16% had alopecia and 38% had previously undiagnosed impaired glucose tolerance (IGT) or diabetes. A significant difference between the four clinic groups existed with regard to menstrual patterns (p = 0.0234), frequency distribution of presenting symptoms and the percentages of patients with PCOS who had already been diagnosed as having PCOS (p = 0.0088). CONCLUSION: This study emphasizes the importance of understanding the full spectrum of PCOS as presented to different specialty clinics. Not only is the syndrome under diagnosed but also are the significant associated morbidities such as IGT and type 2 diabetes. Different specialists need to appreciate the spectrum of health problems for women with PCOS that may extend beyond the specific symptoms that precipitated the initial referral.

Modes of conception and multiple pregnancy: a national survey of babies born during one week in 2003 in the United Kingdom.

OBJECTIVE: To collect data on every baby born in one week in the United Kingdom with respect to mode of conception, multiplicity of pregnancy, and outcome. DESIGN: A questionnaire completed by the midwife birth attendant. SETTING: All maternity units in the United Kingdom. PATIENT(S): All mothers delivering during the week of April 6-12, 2003. INTERVENTION(S): Questionnaire survey. MAIN OUTCOME MEASURE(S): Mode of conception (both spontaneous and assisted), type of fertility treatment, multiplicity of pregnancy, mode of delivery, gestational age, and fetal outcome. RESULT(S): Data were received from 178 maternity units (72.7%) on 6,913 deliveries: 6,812 (98.54%) were singleton, 100 (1.45%) twin, and 1 (0.01%) triplet. In total, 7,015 babies were born. Of all pregnancies, 6,638 (96%) (including the only triplet) were conceived spontaneously and 133 (1.9%) with assistance. The multiple pregnancy rate was significantly greater in assisted (13.5%) than in spontaneous (1.2%) conceptions. Of the multiple pregnancies after fertility treatment, 16.7% resulted from clomifene citrate therapy, 72.2% from IVF or frozen embryo replacements (FET), and 5.6% from superovulation with intrauterine insemination (IUI). The multiple pregnancy rate after IVF/FET (26%) was significantly higher than the one after clomifene citrate therapy (7.3%). In total, 41 babies were born after clomifene citrate therapy, 50 after IVF/ET, and eight after superovulation IUI. The live birth rate was higher for singleton (98.2%) than multiple pregnancies (93.6%). CONCLUSION(S): Multiple pregnancy from IVF and related treatments remains a significant problem and contributes a greater burden than ovulation induction therapies.