Primary hyperparathyroidism in pregnancy: experience of a tertiary centre.

BACKGROUND AND PURPOSE: The management of primary hyperparathyroidism (PHPT) during pregnancy is challenging and there is no clear consensus on whether it increases the risk of complications in pregnancy. We conducted this study to review the maternal and fetal outcomes of pregnant women treated for PHPT in a single centre. METHODS: Data on relevant clinical parameters, demographics, management strategies, maternal and fetal outcomes were collected from the medical records of pregnant patients with PHPT diagnosed between 2012 and 2019. RESULTS: Of 15 pregnant women with PHPT, 6 were managed medically and 9 underwent surgery. The median age at their index pregnancy was 28 years [range 19-42]. The median highest adjusted calcium level in the medical group was 2.90 [range 2.61-3.25] mmol/L vs. 3.11 [2.78-4.95] mmol/L in the surgical group. There was one miscarriage and the stillbirth of twins in the medical group, but no such outcomes in the surgical group. The median gestational ages were 39 + 3 weeks [range 24 + 2-41 + 2 weeks] and 39 + 4 weeks [range 37 + 1-39 + 5 weeks] in the medical and surgical groups, respectively. No birth was complicated by neonatal tetany or convulsions. CONCLUSION: More complications developed in the pregnant PHPT patients who were managed medically than in those who underwent surgery. Surgery performed during the second trimester resulted in good outcomes. Multi-centre prospective studies are required to ascertain the risk of various complications in women with PHPT during pregnancy.

Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis.

BACKGROUND: The reproductive impact of adenomyosis and endometriosis is widely researched but the extent of these impacts remains elusive. It has been demonstrated that endometriosis, in particular, is known to result in subfertility but endometriosis and adenomyosis are increasingly linked to late pregnancy complications such as those caused by placental insufficiency. At the molecular level, the presence of ectopic endometrium perturbs the endometrial hormonal, cellular, and immunological milieu, negatively influencing decidualization, placentation, and developmental programming of the embryo. It is unclear if and how such early aberrant reproductive development relates to pregnancy outcomes in endometriosis and adenomyosis. OBJECTIVE AND RATIONALE: The aims of this systematic review and meta-analysis were to (i) investigate the association of adenomyosis and endometriosis with fertility, obstetric, and neonatal outcomes of women through both assisted reproduction and natural conception and (ii) determine whether endometriosis disease subtypes have specific impacts on different stages of the reproductive process. SEARCH METHODS: A systematic literature review of NHS evidence electronic databases and the Cochrane database identified all comparative and observational studies between 1980 and December 2018 in any language on adenomyosis and endometriosis with fertility, obstetric, and neonatal outcomes (23 search terms used). A total of 104 papers were selected for data extraction and meta-analysis, with use of Downs and Black standardized checklist to evaluate quality and bias. OUTCOMES: We found that endometriosis consistently leads to reduced oocyte yield and a reduced fertilization rate (FR), in line with current evidence. Milder forms of endometriosis were most likely to affect the fertilization (FR OR 0.77, CI 0.63-0.93) and earlier implantation processes (implantation rate OR 0.76, CI 0.62-0.93). The more severe disease by American Society for Reproductive Medicine staging (ASRM III and IV) influenced all stages of reproduction. Ovarian endometriosis negatively affects the oocyte yield (MD -1.22, CI -1.96, -0.49) and number of mature oocytes (MD -2.24, CI -3.4, -1.09). We found an increased risk of miscarriage in both adenomyosis and endometriosis (OR 3.40, CI 1.41-8.65 and OR 1.30, CI 1.25-1.35, respectively), and endometriosis can be associated with a range of obstetric and fetal complications including preterm delivery (OR 1.38, CI 1.01-1.89), caesarean section delivery (OR 1.98 CI 1.64-2.38), and neonatal unit admission following delivery (OR 1.29, CI 1.07-1.55). WIDER IMPLICATIONS: Adenomyosis and the subtypes of endometriosis may have specific complication profiles though further evidence is needed to be able to draw conclusions. Several known pregnancy complications are likely to be associated with these conditions. The complications are possibly caused by dysfunctional uterine changes leading to implantation and placentation issues and therefore could potentially have far-reaching consequences as suggested by Barker's hypothesis. Our findings would suggest that women with these conditions should ideally receive pre-natal counselling and should be considered higher risk in pregnancy and at delivery, until evidence to the contrary is available. In order to expand our knowledge of these conditions and better advise on future management of these patients in reproductive and maternal medicine, a more unified approach to studying fertility and reproductive outcomes with longer term follow-up of the offspring and attention to the subtype of disease is necessary.

Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.

BACKGROUND: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-estrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists directly and rapidly inhibit gonadotropin release within several hours through competitive binding to pituitary GnRH receptors. This property allows their use at any time during the follicular phase. Several different regimes have been described including multiple-dose fixed (0.25 mg daily from day six to seven of stimulation), multiple-dose flexible (0.25 mg daily when leading follicle is 14 to 15 mm), and single-dose (single administration of 3 mg on day 7 to 8 of stimulation) protocols, with or without the addition of an oral contraceptive pill. Further, women receiving antagonists have been shown to have a lower incidence of ovarian hyperstimulation syndrome (OHSS). Assuming comparable clinical outcomes for the antagonist and agonist protocols, these benefits would justify a change from the standard long agonist protocol to antagonist regimens. This is an update of a Cochrane review first published in 2001, and previously updated in 2006. OBJECTIVES: To evaluate the effectiveness and safety of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception cycle SEARCH STRATEGY: We performed electronic searches of major databases, for example Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL, MEDLINE, EMBASE (from 1987 to April 2010); and handsearched bibliographies of relevant publications and reviews, and abstracts of major scientific meetings, for example the European Society of Human Reproduction and Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM). A date limited search of Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL from April 2010 to April 2011 was run. Eighteen studies have been entered into the Classification pending references section of this update. These studies will be appraised for inclusion or exclusion in the next update of this review, due April 2012. SELECTION CRITERIA: Two review authors independently screened the relevant citations for randomised controlled trials (RCTs) comparing different agonist versus antagonist protocols in women undergoing IVF or ICSI. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial risk of bias and extracted data. If relevant data were missing or unclear, the authors were contacted for clarification. MAIN RESULTS: Forty-five RCTs (n = 7511) comparing the antagonist to the long agonist protocols fulfilled the inclusion criteria. There was no evidence of a statistically significant difference in rates of live-births (9 RCTs; odds ratio (OR) 0.86, 95% CI 0.69 to 1.08) or ongoing pregnancy (28 RCTs; OR 0.87, 95% CI 0.77 to 1.00). There was a statistically significant lower incidence of OHSS in the GnRH antagonist group (29 RCTs; OR 0.43, 95% CI 0.33 to 0.57). AUTHORS' CONCLUSIONS: The use of antagonist compared with long GnRH agonist protocols was associated with a large reduction in OHSS and there was no evidence of a difference in live-birth rates.

Follicular phase endocrine characteristics during ovarian stimulation and GnRH antagonist cotreatment for IVF: RCT comparing recFSH initiated on cycle day 2 or 5.

CONTEXT: Strategies involving mild ovarian stimulation protocols for in vitro fertilization (IVF) might lessen discomfort to the patient and substantially lower complication rates. OBJECTIVE: The objective of the study was to compare the follicular-phase endocrine characteristics and follicular development in patients who started recombinant FSH (recFSH) on cycle day (CD) 2 or CD5 in IVF treatment, using GnRH antagonist as comedication. DESIGN: This was a prospective randomized controlled trial in two university centers in Belgium and The Netherlands. PATIENTS: Seventy-six IVF/intracytoplasmic sperm injection patients were included in the study. INTERVENTIONS: The control group (CD2) received a standard treatment with 150 IU recFSH from CD2, whereas in the study group (CD5), stimulation was started on d 5 of the cycle. The GnRH antagonist was administered daily from CD6 onward in both treatment arms. MAIN OUTCOME MEASURE: Endocrine follicular phase profile during ovarian stimulation was measured. RESULTS: Follicular-phase patterns of gonadotropin and steroid concentrations were found to be comparable in both treatment groups, except for serum estradiol being significantly higher in the CD2 group on d 6 of the cycle (295.6 ± 202.5 ng/liter in the CD2 vs. 102.5 ± 47.9 ng/liter in the CD5 group; P < 0.01) and LH being significantly higher in the CD5 group on d 6 of the cycle (1.7 ± 0.7 IU/liter in the CD2 vs. 5.0 ± 2.1 IU/liter in the CD5 group; P < 0.01). With regard to follicular development, there was no difference in the numbers of small follicles (<10 mm), intermediate follicles (10-12 and > 12-14 mm) and large follicles (>14 mm) in both groups. CONCLUSIONS: This study shows that the administration of recFSH starting on d 2 or d 5 of the cycle in a GnRH antagonist protocol for IVF/intracytoplasmic sperm injection patients yields a comparable endocrine profile and follicular development. Future studies should focus on the design of more patient-tailored ovarian stimulation protocols.

Alpha-synuclein expression in the developing human brain.

Alpha (alpha)-synuclein is a presynaptic protein, abnormal expression of which has been associated with neurodegenerative and neoplastic diseases. It is abundant in the developing vertebrate central nervous system (CNS), but less is known about its developmental expression in the human CNS. Immunohistochemical expression of alpha-synuclein was studied in 39 fetal, perinatal, pediatric, and adolescent brains. Perikaryal expression of alpha-synuclein is observed as early as 11-wk gestation in the cortical plate. Several discrete neuronal groups in the hippocampus, basal ganglia, and brain stem express perikaryal alpha-synuclein by 20-wk gestation, persisting through the first few years of life. In the cerebellum, alpha-synuclein is present by 21-wk gestation and persists into adult life as a coarse granular neuropil reaction product in the internal granular layer, and as a diffuse neuropil "blush" in the molecular layer. The germinal matrix, glia, endothelial cells, external granular layer, Pukinje cells, and dentate neurons are consistently negative for alpha-synuclein. We conclude that alpha-synuclein is expressed very early in human gestation, and that its distribution and temporal sequence of expression varies in discrete neuronal groups. Perikaryal alpha-synuclein starts disappearing from the neuronal cytosol in early childhood, and only the neuropil retains immunoreactivity into adulthood. The reappearance of alpha-synuclein in the adult neuronal cytosol in certain disease processes may represent reemergence of cues from an earlier developmental stage as part of a stress response.