The acrosome index, radical buffer capacity and number of isolated progressively motile spermatozoa predict IVF results

BACKGROUND: The accuracy by which a number of newly described semen variables can predict either total fertilization failure (TFF) or pregnancy outcome in IVF, has not previously been investigated. The study aim was, therefore, to determine prospectively the predictive value of these variables. METHODS: The semen variables investigated were the post-wash total progressively motile sperm cell count (TPMC(post-wash)), the acrosome index (AI), 'cytoplasmic residues' and normal sperm morphology, evaluated according to the strict criteria ('strict criteria'), as well as the fast and slow total radical trapping antioxidant potential ('fast TRAP' and 'slow TRAP' respectively). RESULTS: The study group (n = 87) showed a mean (+/- SD) number of 10.2 +/- SD retrieved oocytes, 12.6% TFF, a mean fertilization rate of 59.7% and a pregnancy rate of 19.5% (17/87). TFF was significantly predicted by TPMC(post-wash), 'strict criteria', AI and 'cytoplasmic residues' (all P < 0.05). The outcome after embryo transfer was significantly predicted by AI and 'fast TRAP'. Semen samples with an AI <5% and a 'fast TRAP' <1.14 mmol/l in particular did not result in any pregnancies after IVF-embryo transfer. CONCLUSIONS: Of all the measured and calculated semen variables, TPMC(post-wash) was the best predictor of TFF, whilst AI and 'fast TRAP' were the best predictors of pregnancy after IVF.     

Mild thyroid abnormalities and recurrent spontaneous abortion: diagnostic and therapeutical approach

PROBLEM: The aim of this study is to evaluate the role of mild thyroid abnormalities in recurrent spontaneous abortion, and to assess the effects of two different therapeutical protocols. METHOD: A prospective study in the population of recurrent aborters with mild thyroid abnormalities, evaluating the obstetric outcome in 42 patients. Sixteen thyroid autoantibodies positive patients were treated with thyroid replacement therapy, while 11 patients received intravenous immunoglobulins (IVIG). Fifteen patients, characterized by negative antithyroid antibodies, and having underlying thyroid pathology, were treated with thyroid replacement therapy. RESULTS: Among patients with thyroid antibodies, 6 out of the 11 pregnancies (54.5%) treated with IVIG ended in live birth. In the thyroid supplementation group, 13 out of 16 pregnancies (81.2%) ended in live birth. Only one pregnancy loss occurred among patients with a mild underlying thyroid pathology treated with thyroid replacement therapy. CONCLUSIONS: Mild thyroid abnormalities are associated with an increased rate of miscarriage. This poor obstetrical prognosis seems to be related to an impaired thyroid adaptation to pregnancy. Thyroid replacement therapy appears to be more effective than IVIG in preventing a new miscarriage.     

Plasma antiviral activity and interferon-gamma production by superantigen-stimulated lymphocytes during normal human pregnancy

PROBLEM: Plasma interferon (IFN)-beta levels, lymphocyte responsiveness, and evaluation of the relationship between circulating antiviral activity (AA) and IFN-gamma production were studied in pregnant women and nonpregnant age-matched controls with the objective of elucidating the downregulation of IFN-gamma production in successful pregnancy. METHOD OF STUDY: In plasma and supernatants of peripheral blood mononuclear cell (PBMC) cultures, stimulated with staphylococcal enterotoxin A (SEA) superantigen, from 43 pregnant women with a history of normal pregnancy and 30 healthy nonpregnant age-matched controls, levels of AA were measured in a micromethod by inhibition of the cytopathic effect (CPE) caused by vesicular stomatitis virus (VSV) in the human amnionic cell line (WISH). RESULTS: Significantly higher plasma AA (60% was IFN-gamma and residual activity was acid-labile IFN-like) was present in pregnant women than controls. On the other hand, SEA-activated PBMCs from pregnant women produced significantly lower IFN-gamma levels than those of nonpregnant women. Furthermore, maternal plasma AA levels correlated negatively with IFN-gamma production by SEA-stimulated PBMCs. CONCLUSION: The hypothesis that successful pregnancy requires downregulation of IFN-gamma is only partially sustained, suggesting that the immunology of pregnancy is more complex and that murine and human pregnancy have different cytokine profiles.     

Delay between pregnancy confirmation and sickle cell and [corrected] thalassaemia screening: a population-based cohort study.

BACKGROUND: Antenatal sickle cell and thalassaemia screening sometimes occurs too late to allow couples a choice regarding termination of affected fetuses. The target gestational age for offering the test in the UK is 10 weeks. AIM: To describe the proportion of women screened before 70 days' (10 weeks') gestation and the delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening. DESIGN OF STUDY: Cohort study of reported pregnancies. SETTING: Twenty-five general practices in two UK inner-city primary care trusts offering universal screening. METHOD: Anonymised data on all pregnancies reported to participating general practices was collected for a minimum of 6 months. RESULTS: There were 1441 eligible women intending to proceed with their pregnancies, whose carrier status was not known. The median (interquartile range [IQR]) gestational age at pregnancy confirmation was 7.6 weeks (6.0-10.7 weeks) and 74% presented before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR = 12.6-18.0 weeks), with only 4.4% being screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7-9.3 weeks) After allowing for practice level variation, there was no association between delay times and maternal age, parity, and ethnic group. CONCLUSION: About 74% of women consulted for pregnancy before 10 weeks' gestation but fewer than 5% of women were screened before the target time of 10 weeks. Reducing the considerable delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening requires methods of organising and delivering antenatal care that facilitate earlier screening to be developed and evaluated.     

Pre-term birth and severe pre-eclampsia are not associated with altered expression of HLA on human trophoblasts

PROBLEM: The unusual pattern of human leukocyte antigen (HLA) expression on human trophoblasts could play an important role in successful pregnancy outcome. To determine whether alterations in HLA expression are associated with pregnancy abnormalities we have investigated expression of these antigens on chorionic and extravillous cytotrophoblasts. METHODS: Frozen tissue sections of placenta and fetal membranes were collected after pre-term spontaneous delivery, severe pre-eclampsia pre-term Caesarean section, normal term delivery and term Caesarean section. HLA expression was analyzed by immunohistochemistry. RESULTS: We did not observe differences in the expression of HLA on chorionic and extravillous cytotrophoblasts in pregnancy abnormalities. However, we noted higher expression levels of HLA class Ia molecules in amnion epithelial cells in pre-term deliveries. Furthermore, in severe pre-eclampsia the number of extravillous cytotrophoblast islands were elevated when compared with pre-term deliveries. CONCLUSIONS: No alterations in expression of HLA class Ia, HLA-G and HLA class II on human trophoblasts in pregnancy abnormalities were seen.     

Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation

A 3 year retrospective analysis was conducted of pregnancies achieved after various assisted reproductive treatment modalities in our infertility practice, to calculate and compare the rates of monozygotic twinning (MZT). A total of 731 pregnancies achieved after various assisted reproduction treatments were reviewed. Gonadotrophin therapy for induction of ovulation and controlled ovarian hyperstimulation (COH) yielded 129 clinical pregnancies. Conventional IVF yielded 139 pregnancies. IVF and intracytoplasmic sperm injection (ICSI) with or without assisted hatching (AH) yielded 463 pregnancies, all during the same time period. The rates of multiple pregnancy (monozygotic and dizygotic) twins and triplets were recorded. MZT was found in 1.5% of ovulation induction or COH pregnancies (2/129). The incidence of MZT after conventional IVF was 0.72% (1/139). After IVF-ICSI/AH, MZT was found in 0.86% (4/463). The overall rate of MZT was 0.95% (7/731). Five cases were dizygotic triplets and two cases were monozygotic twins. We found the rate of MZT after assisted reproduction treatment increased more than two-fold over the background rate in the general population. Dizygotic triplets were found more often than monozygotic twins. The rate of MZT was consistently increased, irrespective of treatment modality or micromanipulation. This may signify that the aetiology of increased MZT after assisted reproduction is the gonadotrophin treatment rather than in-vitro conditions, micromanipulation, or multiple embryo transfer.     

Dimethyl sulfoxide elevates intracellular Ca2+ and mimics effects of increased light intensity in a photoreceptor

A 1% (v/v) solution of dimethyl sulfoxide (DMSO) added to the saline bath of isolated Balanus eburneus photoreceptors increased receptor potential amplitude by 40–50% and shortened time to peak amplitude and latency by 20–25%. The light-sensitive membrane current of voltage-clamped cells was increased systematically as DMSO concentration was increased from 1% to 10%. The null potential of the light sensitive current was unaffected by DMSO with short pulses of light, indicating that DMSO has no direct effect on ion selectivity of the light-sensitive channel. Absorbance changes of cell injected with the calcium indicator arsenazo III show that DMSO elevates intracellular Ca²⁺ (Ca_i). Current-voltage relations in darkness reveal that DMSO induces a small sustained inward current (5 nA) which has a null potential similar to the lightinduced current. DMSO may activate the light-sensitive conductance via the increase in Ca_i However, the altered kinetics and increased amplitude of the receptor current are opposite to the desensitizing effects normally observed with increased Ca_i.     

The cumulative embryo score: a predictive embryo scoring technique to select the optimal number of embryos to transfer in an in-vitro fertilization and embryo transfer programme.

In order to achieve a clinical pregnancy rate higher than that achieved following initial adoption of in-vitro fertilization embryo transfers, more than one embryo is transferred. This has led to a substantial increase in unwanted multiple pregnancy rates with IVF as compared with natural conception. What is therefore required is a simple, clinically useful embryo scoring system, to reflect embryo developmental potential, which will enable the selection of the optimal number of embryos to transfer in order to achieve the maximum pregnancy rate with a low incidence of high order multiple pregnancies. We believe that the Cumulative Embryo Score (CES) achieves these aims. On the day of embryo transfer the grade of each embryo transferred was multiplied by the number of blastomeres to produce a score for each embryo, and summation of the scores obtained for all the embryos transferred gave the CES. The grouped pregnancy rates obtained rose as the CES increased to maximum of 42. A continued increase in the CES above 42 did not result in any further rise in the pregnancy rate. However, an analysis of all our IVF pregnancies showed that the multiple pregnancy rate continued to rise above a CES of 42. By restricting the CES per embryo transfer to 42, 78% of triplet pregnancies and 100% of the quadruplet IVF pregnancies could have been predicted and potentially avoided.     

Continuous administration of gonadotrophin-releasing hormone agonist during the luteal phase in IVF

BACKGROUND: It has been reported that ceasing the administration of gonadotrophin-releasing hormone (GnRH) agonist causes a profound suppression of circulating serum gonadotrophins. A comparative prospective and randomized study was conducted to investigate the effect of continuous administration of GnRH agonist during the luteal phase in an ovarian stimulation programme for IVF. METHODS: GnRH agonist was administered intranasally from the midluteal phase of the previous cycle, and pure FSH administration started on cycle day 7. In the continuous-long protocol (cL) group (n = 161 ), GnRH agonist administration was continued until 14 days after oocyte retrieval. In the long protocol (L) group (n = 158 ), GnRH agonist was administered until the day before human chorionic gonadotrophin (HCG) administration. RESULTS: The implantation rate and live birth rate per unit of transferred embryos were significantly higher in the cL group than the L group (P < 0.05 ). Serum LH and FSH concentrations on the day of, and 1 day after, HCG administration were significantly lower in the L group than the cL group (P < 0.01 ). CONCLUSIONS: Continuation of GnRH agonist administration during the luteal phase might facilitate implantation, and prevent the profound suppression of serum gonadotrophins.     

新洁尔灭对小白鼠抗早孕的病理组织学观察

本文报告用不同剂量的新洁尔灭和同体积生理盐水注入怀孕5天小白鼠的宫腔内,3天后杀死,观察其蜕膜、胚泡、宫内膜腺体和卵巢黄体病理学改变。实验表明:对照组无改变。实验组小白鼠的蜕膜细胞全部退变坏死。病变随着给药量的递增而渐趋严重;同时胚泡亦有退变和坏死。提示:新洁尔灭对早期妊娠小白鼠是有抗早孕效果的。根据实验结果,我们认为新洁尔灭对小白鼠抗早孕的机制,很可能是一个综合因素,有直接的,也有间接的。作者强调在抗早孕机制诸因素中,蜕膜退变坏死是一个重要的因素。