BACKGROUND

Endothelins (EDNs) are thought to modulate endometrial blood flow during menses, stromal healing and endometrial growth during the proliferative phase. Our goal was to assess the effects of estrogen and progesterone on the EDN paracrine system in the endometrium of rhesus macaques.

METHODS

In this study, archived samples were used. These samples were collected from oophorectomized rhesus macaques that were treated sequentially with estradiol (E₂) and then E₂ plus progesterone to create artificial menstrual cycles. Endometrium from animals in the menstrual, proliferative and secretory phases of the artificial cycle were analyzed by real-time PCR, in situ hybridization and immunocytochemistry to detect changes in EDN peptides (EDN1, EDN2, EDN3), EDN receptors (EDNRA, EDNRB), EDN-converting enzyme 1 (ECE1) and membrane metalloendopeptidase (MME)—an enzyme that degrades the EDNs.

RESULTS

Compared with the late secretory phase, progesterone withdrawal at the end of the artificial menstrual cycle triggered an increase (P< 0.05) in EDN1, EDNRB and ECE1 in the upper functionalis zone during menses of the next cycle. Treatment with E₂ alone in the proliferative phase increased (P< 0.05) EDNRA transcript, which was confined predominantly to the stromal cells. E₂ plus progesterone in the artificial secretory phase suppressed (P< 0.05) the expression of EDN3 in the functionalis zone stroma and epithelia, tended (P= 0.08) to attenuate levels of epithelial EDN2 and markedly up-regulated (P< 0.05) the stromal expression of MME.

CONCLUSIONS

Our results indicate that estrogen and progesterone regulate the EDN family during the menstrual cycle. The changes in the EDN paracrine system during the mid-secretory phase may indicate a role for EDN during embryo implantation.

BACKGROUND

To determine the optimal surgical approach for laparoscopic uterine artery ligation (LUAL) combined with myomectomy in the management of women with symptomatic uterine fibroids.

METHODS

This is a prospective study. One hundred and six women with symptomatic uterine myomas underwent LUAL + laparoscopic morcellation after enucleation (enucleation group) (n = 51) or LUAL + laparoscopic in situ morcellation (ISM group) (n = 55). The outcome was measured by comparing surgical techniques, symptom control, recurrence and pregnancy during a 3-year follow-up in both groups.

RESULTS

General characteristics of the patients were similar in both groups, except the myomas were larger in the ISM group. The operative time (mean ± SD) was significantly shorter in the ISM group than the enucleation group (107 ± 30 min versus 128 ± 49 min, P = 0.009). There were no differences in the therapeutic outcomes of the two groups at the 3-year follow-up, with low recurrence rates and good symptom control rates. Of the sexually active patients without contraception, the pregnancy and live birth rates were 87.5 and 100% in the ISM group and 66.7 and 83.3% in the enucleation group (all NS).

CONCLUSIONS

The LUAL + myomectomy, either by enucleation or ISM, is acceptable in the management of symptomatic uterine fibroids. However, the LUAL + ISM technique might be more feasible, as it requires less operative time.

BACKGROUND

Hysterectomy guidelines highlight an increase in urinary tract injuries with laparoscopic hysterectomy (LH). This national survey analyses complications of LH, abdominal hysterectomy (AH) and vaginal hysterectomy (VH).

METHODS

A prospective cohort undergoing hysterectomy for benign indications during 2006 was drawn from 53 hospitals in Finland; all communal hospitals participated. Detailed questionnaires covered surgical data and intra- and post-operative major and minor complications, for which risk factors were analysed by a multivariate logistic regression model adjusted for surgical data and patient characteristics.

RESULTS

Major complications rates in AH (n= 1255, 24%), LH (1679, 32%) and VH (2345, 44%) were 4.0, 4.3 and 2.6%, and total complications rates were 19.2, 15.4 and 11.7%, respectively. Logistic regression showed no statistically significant differences between approaches for any organ injuries or other major complications. Most bladder and bowel injuries (88 and 83%), but not ureter injuries (10%), were recognized intra-operatively. The ureter injury rate was low after LH (0.3%), as it was after other types of hysterectomy. Compared with LH, AH increased the odds of wound infection, and was an independent risk factor for urinary infections and febrile events. Compared with AH, LH and VH both presented a higher risk for pelvic infection; surgically treated equally often regardless of the type of hysterectomy. No differences in complications emerged between LH and VH. Obesity was a risk factor for many infections. Surgical adhesiolysis [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.38–4.21] was the strongest single risk factor for major complications as a whole. Bladder injury was associated with a history of caesarean section (OR 4.01, 95% CI 2.06–7.83) and with a large uterus ≥500 g (OR 2.88, 95% CI 1.05–7.90), while bowel injury was associated with adhesiolysis (OR 29.07, 95% CI 7.17–117.88).

CONCLUSIONS

FINHYST is a large prospective hysterectomy study illustrating actual complications. Whenever possible, hysterectomy should be minimally invasive.

BACKGROUND

Safety concerns have been expressed regarding the use of immature non-ejaculated spermatozoa for ICSI. Therefore, adverse health outcomes, birth parameters, major anomaly rates and chromosomal aberrations in children born after ICSI using testicular and epididymal sperm were investigated.

METHODS

Questionnaire data and results of physical examinations of 530 children born after ICSI with testicular sperm and of 194 children born after ICSI with epididymal sperm were compared with data on 2516 ICSI children born using ejaculated sperm.

RESULTS

Birth parameters, stillborn rates, prematurity rates and rates of low birthweight and very low birthweight were comparable between the non-ejaculated and the ejaculated sperm groups. The perinatal death rate was higher for twins but not for singletons in the non-ejaculated sperm group in comparison to the control cohort of children born using ejaculated sperm. A non-significant increase in major anomalies was reported in the non-ejaculated sperm group in comparison to the ejaculated sperm group. No more anomalies were observed in pre- and post-natal karyotypes from viable pregnancies established using non-ejaculated sperm versus ejaculated sperm.

CONCLUSION

Overall neonatal health in terms of birth parameters, major anomalies and chromosomal aberrations in our large cohort of children born by the use of non-ejaculated sperm seems reassuring in comparison to the outcome of children born after the use of ejaculated sperm.

BACKGROUND

Assisted hatching (AH) is a manipulation of zona pellucida aiming to facilitate embryo implantation.

METHODS

Systematic review and meta-analysis of medical literature was used to evaluate the effect of AH on assisted reproduction outcomes: clinical pregnancy, live birth, multiple pregnancy and miscarriage. Additional analysis was performed in these subgroups: (i) fresh embryos transferred to unselected or non-poor prognosis women; (ii) fresh embryos transferred to women with previous repeated failure; (iii) fresh embryos transferred to women of advanced age; (iv) frozen-thawed embryos transferred to unselected or non-poor prognosis women. Analyses were based on risk ratio and 95% confidence intervals (RR, 95% CIs) using Mantel–Haenszel random effects model.

RESULTS

There were 28 studies (5507 participants) included. AH was related to a trend toward increased clinical pregnancy for all participants (RR = 1.11, 95% CI = 1.00–1.24), with a significant increase in subgroups 2 (RR = 1.73; 95% CI = 1.37–2.17) and 4 (RR = 1.36; 95% CI = 1.08–1.72, P< 0.01), but not for subgroups 1 and 3. For multiple pregnancy, a significant increase was observed for all participants (RR = 1.45; 95% CI = 1.11–1.90) and for subgroups 2 (RR = 2.53; 95% CI = 1.23–5.21) and 4 (RR = 3.40; 95% CI = 1.93–6.01). No significant heterogeneity was observed in subgroup analysis.

CONCLUSIONS

AH was related to increased clinical pregnancy and multiple pregnancy rates in women with previous repeated failure or frozen-thawed embryos. However, AH is unlikely to increase clinical pregnancy rates when performed in fresh embryos transferred to unselected or non-poor prognosis women or to women of advanced age. Due to the small sample evaluated by the pool of included studies, no proper conclusions could be drawn regarding miscarriage or live birth.

BACKGROUND

To evaluate the safety of ICSI with epididymal sperm, this study compared children born after ICSI treatment with epididymal sperm and children conceived after IVF and ICSI with ejaculated sperm. Additionally, the results of a multidisciplinary, multicentre follow-up of the children conceived with epididymal sperm at 2 years of age are described.

METHODS

This follow-up study included 378 children conceived after ICSI with epididymal sperm (percutaneous epididymal sperm aspiration: PESA group) and a control group of 1192 IVF and 1126 ICSI (with ejaculated sperm) children, all with a gestational age of 20 weeks or more. Questionnaires were sent at birth, 1 year and 4 years of age, collecting data on parental, pregnancy and child factors. A total of 148 PESA children were assessed at 2 years of age for motor performance, mental- and language development and compared with the Dutch norms.

RESULTS

PESA children showed no increased risks for stillbirths, total deaths and malformations. They also did not differ from IVF and ICSI children in gender rate, birthweight and gestational age. The mental Bayley score was higher (P < 0.05) for PESA singletons and parents reported fewer (P < 0.05) behavioural problems in the PESA group than the Dutch reference group. The scores for syntactic and lexical development for the PESA singletons were better (P < 0.05) than the Dutch standards.

CONCLUSIONS

ICSI with epididymal sperm does not lead to more stillbirths or congenital malformations in comparison to IVF and ICSI with ejaculated sperm and does not lead to poor development in comparison with the Dutch reference group.

BACKGROUND

Preimplantation genetic screening (PGS) has increasingly been used in the past decade. Here we present a systematic review and meta-analysis of RCTs on the effect of PGS on the probability of live birth after IVF.

METHODS

PubMed and trial registers were searched for RCTs on PGS. Trials were assessed following predetermined quality criteria. The primary outcome was live birth rate per woman, secondary outcomes were ongoing pregnancy rate, miscarriage rate, multiple pregnancy rate and pregnancy outcome.

RESULTS

Nine RCTs comparing IVF with and without PGS were included in our meta-analysis. Fluorescence in situ hybridization was used in all trials and cleavage stage biopsy was used in all but one trial. PGS significantly lowered live birth rate after IVF for women of advanced maternal age (risk difference: –0.08; 95% confidence interval: –0. 13 to –0.03). For a live birth rate of 26% after IVF without PGS, the rate would be between 13 and 23% using PGS. Trials where PGS was offered to women with a good prognosis and to women with repeated implantation failure suggested similar outcomes.

CONCLUSIONS

There is no evidence of a beneficial effect of PGS as currently applied on the live birth rate after IVF. On the contrary, for women of advanced maternal age PGS significantly lowers the live birth rate. Technical drawbacks and chromosomal mosaicism underlie this inefficacy of PGS. New approaches in the application of PGS should be evaluated carefully before their introduction into clinical practice.

BACKGROUND

Complex chromosomal rearrangements (CCRs) describe structural rearrangements, essentially translocations, involving at least three breakpoints on two or more chromosomes. Although they are rare in humans, their clinical identification is important since CCR carriers can display various phenotypes which include phenotypically normal subjects, infertile males and patients with mental retardation and/or congenital abnormalities. The rearrangement can be de novo or familial. The use of fluorescent in situ hybridization assays and molecular techniques for the characterization of CCRs have indicated that the rearrangements could be more complex than initially assumed. Accumulating data have revealed that the mechanisms underlying the genesis of CCRs remain elusive.

METHODS

We performed a large PubMed search in order to summarize the current knowledge in this field and address important aspects of CCR formation and meiotic behavior, highlighting the complexity of these rearrangements at the chromosomal and genomic level.

RESULTS

The review of published data indicates that the complexity of CCRs is becoming increasingly known, thanks to the application of more and more efficient molecular techniques. These approaches have allowed the precise sequence analysis of breakpoints and the identification of insertions, deletions, inversions and recombination events. New models have been proposed for the formation of CCRs, based on replication-based mechanisms and specific sequence elements. Their meiotic behavior has been discussed in the light of these new molecular data.

CONCLUSIONS

Despite the increasing understanding of the mechanisms involved in their genesis, CCRs arise as unique, complex events for which the genetic and reproductive counseling of carriers remains a challenge.

BACKGROUND

Preimplantation  genetic diagnosis (PGD) has been stated to improve live birth rates compared with natural conception in couples with recurrent miscarriage (RM) carrying a structural chromosome abnormality. It is unclear to what extent this claim can be substantiated by evidence. A systematic review of the literature was performed on the reproductive outcome of these couples after natural conception or after PGD.

METHODS

MEDLINE, EMBASE and the Cochrane database were searched until April 2009. Trials, patient series and case reports describing reproductive outcome in couples with RM carrying a structural chromosome abnormality after natural conception and/or after PGD were included. Since no randomized controlled trials or non-randomized comparative studies were found, separate searches for both groups were conducted. Primary outcome measure was live birth rate per couple. Secondary outcome measure was miscarriage rate per couple.

RESULTS

Four observational studies reporting on the reproductive outcome of 469 couples after natural conception and 21 studies reporting on the reproductive outcome of 126 couples after PGD were found. After natural conception, live birth rate per couple varied between 33 and 60% (median 55.5%) after parental chromosome analysis; miscarriage rate ranged from 21 to 40% (median 34%). After PGD, live birth rate per couple varied between 0 and 100% (median 31%) after parental chromosome analysis; miscarriage rate ranged from 0 to 50% (median 0%).

CONCLUSIONS

Currently, there are insufficient data indicating that PGD improves the live birth rate in couples with RM carrying a structural chromosome abnormality.

BACKGROUND

Aspirin is believed to improve the outcome of IVF, but previous conventional meta-analyses on the subject are conflicting. Therefore, we performed a meta-analysis with individual patient data (IPD MA) of randomized clinical trials (RCTs) on the subject.

METHODS

A systematic literature search was conducted to identify RCTs assessing the effectiveness of aspirin in IVF. Authors were asked to share their original data. In a one step meta-analytic approach, the treatment effect of aspirin was estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression, based on the intention to treat principle.

RESULTS

Ten studies fulfilled the inclusion criteria. Authors of six studies provided IPD, including 1119 patients (562 placebo and 557 aspirin). There were 160 clinical pregnancies in the aspirin (28.8%) and 179 (31.9%) in the placebo group [OR 0.86, 95% CI (0.69–1.1)]. There were 129 ongoing pregnancies in the aspirin (23.6%) and 147 in the placebo group (26.7%) [OR 0.85, 95% CI (0.65–1.1)]. Whereas the conventional meta-analysis limited to studies that could provide IPD showed an OR of 0.89 (95% CI 0.69–1.2), the conventional meta-analysis limited to the eight studies of which method of randomization could be confirmed showed an OR of 0.94 (95% CI 0.76–1.17) and the conventional meta-analysis including all 10 eligible RCTs identified with our search changed the OR to 1.07 (95% CI 0.81–1.41). This difference in direction of effect, derived from the studies not able to share IPD of which quality of randomization could not be confirmed.

CONCLUSIONS

Aspirin does not improve pregnancy rates after IVF.

BACKGROUND

Patients with polycystic ovary syndrome (PCOS) are at risk of arterial disease. We examined the risk of (non)fatal coronary heart disease (CHD) or stroke in patients with PCOS and ovulatory women without PCOS, and assessed whether obesity might explain a higher risk of CHD or stroke.

METHODS

We performed a systematic review and meta-analysis of controlled observational studies. Four definitions of PCOS were considered: World Health Organization type II anovulation, National Institutes of Health criteria, Rotterdam consensus and Androgen-excess criteria. Obesity was defined as BMI > 30 kg/m² and/or waist circumference >88 cm. Study quality was assessed using the Newcastle–Ottawa Scale. Primary outcome was fatal/non-fatal CHD or stroke. Definitions of CHD and stroke were based on criteria used by the various authors. The effect measure was the pooled relative risk in a random effects model. Risk ratios and rate ratios were combined here.

RESULTS

After identifying 1340 articles, 5 follow-up studies published between 2000 and 2008 were included. The studies showed heterogeneity in design, definitions and quality. In a random effects model the relative risk for CHD or stroke were 2.02 comparing women with PCOS to women without PCOS (95% confidence interval 1.47, 2.76). Pooling the two studies with risk estimates adjusted for BMI showed a relative risk of 1.55 (1.27, 1.89).

CONCLUSIONS

This meta-analysis showed a 2-fold risk of arterial disease for patients with PCOS relative to women without PCOS. BMI adjustment did not affect this finding, suggesting the increased risk for cardiovascular events in PCOS is not completely related to a higher BMI in patients with PCOS.

BACKGROUND

GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering.

METHODS

This narrative review is based on expert presentations and subsequent group discussions supplemented with publications from literature searches and the authors’ knowledge. Moreover, randomized controlled trials (RCTs) were identified and analysed either in fresh IVF cycles with embryo transfer (ET), oocyte donation cycles or cycles without ET; risk differences were calculated regarding pregnancy rate and OHSS rate.

RESULTS

In fresh IVF cycles with ET (9 RCTs) no OHSS was reported after GnRHa triggering [0% incidence in the GnRHa group: risk difference 5% (with 95% CI: –0.07 to 0.02)]. Importantly, the delivery rate improved significantly after modified luteal support [6% risk difference in favour of the HCG group (95% CI: –0.14 to 0.2)] when compared with initial studies with conventional luteal support [18% risk difference (95% CI: –0.36 to 0.01)]. In oocyte donation cycles (4 RCTs) the OHSS incidence is 0% [10% risk difference (95% CI: 0.02–0.40)].

CONCLUSIONS

GnRHa triggering is a valid alternative to hCG triggering, resulting in an elimination of OHSS. After modified luteal support there is now a non-significant difference of 6% in delivery rate in favour of hCG triggering.

BACKGROUND

A limitation to our ability to distinguish between developmentally competent and incompetent eggs is our still only partial knowledge of the critical features that are needed to make a good egg and when during oogenesis these specific characteristics are acquired. The main objective of this review is to summarize the results of areas of investigation that are contributing to our still inadequate understanding of the molecular aspects of making developmentally competent eggs.

METHODS

For each area discussed, a systematic search was made using PubMed. The search was without temporal limits but mainly yielded publications between 1982–1999 (23%) and 2000–2011 (77%).

RESULTS

Taking an oocyte-centred view, we describe throughout folliculogenesis: (i) the factors that regulate oocyte growth; (ii) the role of oocyte–cumulus cell dialogue; (iii) the epigenetic organization of the oocyte genome and (iv) the storage and regulation of maternal RNAs.

CONCLUSIONS

The multifaceted complex of factors involved in oocyte growth constitutes the backbone on which oocyte developmental competence is built up. Operating behind the expression of these factors is a specific epigenetic signature established during oogenesis, but our knowledge is only approximate and major efforts will be required for more accurate analyses at specific gene loci. The growing research on small silencing RNAs during oogenesis and early oocyte development is revealing these molecules’ critical role in mRNA degradation. Our next challenge will be to dissect the complex interactions among the different molecular players identified and to establish the presence of functional links among these factors.

BACKGROUND

The majority of research aimed at improving embryo development in vitro has focused on manipulation of the chemical environment, examining details such as energy substrate composition and impact of various growth factors or other supplements. In comparison, relatively little work has been done examining the physical requirements of preimplantation embryos and the role culture platforms or devices can play in influencing embryo development.

METHODS

Electronic searches were performed using keywords centered on embryo culture techniques using PUBMED through June 2010 and references were searched for additional research articles.

RESULTS

Various approaches to in vitro embryo culture that involve manipulations of the physical culture environment are emerging. Novel culture platforms being developed examine issues such as media volume and embryo spacing. Furthermore, methods to permit dynamic embryo culture with fluid flow and embryo movement are now available, and novel culture surfaces are being tested.

CONCLUSIONS

Although several factors remain to be studied to optimize efficiency, manipulations of the embryo culture microenvironment through novel culture devices may offer a means to improve embryo development in vitro. Reduced volume systems that reduce embryo spacing, such as the well-of-the-well approach, appear beneficial, although more work is needed to verify the source of their true benefit in human embryos. Emerging microfluidic technology appears to be a promising approach. However, along with the work on specialized culture surfaces, more information is required to determine the impact on human embryo development.

BACKGROUND

Approximately half recurrent miscarriage (RM) cases remain unexplained after standard investigations. Secondary RM (SRM) is, in contrast to primary RM, preceded by a birth, which increases the transfer of fetal cells into the maternal circulation. Mothers of boys are often immunized against male-specific minor histocompatibility (H-Y) antigens, and H-Y immunity can cause graft-versus-host disease after stem-cell transplantation. We proposed the H-Y hypothesis that aberrant H-Y immunity is a causal factor for SRM.

METHODS

This is a critical review of the H-Y hypothesis based on own publications and papers identified by systematic PubMed and EMBASE searches.

RESULTS

SRM is more common after the birth of a boy and the subsequent live birth rate is reduced for SRM patients with a firstborn boy. The male:female ratio of children born prior and subsequent to SRM is 1.49 and 0.76 respectively. Maternal carriage of HLA-class II alleles presenting H-Y antigens to immune cells is associated with a reduced live birth rate and increased risk of obstetric complications in surviving pregnancies in SRM patients with a firstborn boy. In early pregnancy, both antibodies against HLA and H-Y antigens are increased in SRM patients compared with controls. Presence of these antibodies in early pregnancy is associated with a lower live birth rate and a low male:female ratio in subsequent live births, respectively. Births of boys are also associated with subsequent obstetric complications in the background population.

CONCLUSIONS

Epidemiological, immunogenetic and immunological studies support the hypothesis that aberrant maternal H-Y immune responses have a pathogenic role in SRM.

BACKGROUND

This study was conducted to identify and characterize repopulating spermatogonial stem cells (SSCs) in the adult human testes.

METHODS

Testes biopsies from obstructive azoospermic patients and normal segments of human testicular tissue were used. Flow cytometry, real-time PCR and immunohistochemical analysis were performed. Purified human spermatogonia were transplanted into busulfan-treated recipient mouse testes and integrated cells were detected by human nuclear protein antibody co-localized with stem cell and germ cell markers.

RESULTS

Testicular biopsies collected from obstructive azoospermic men showed similar morphology and distribution of markers to the normal human testes. Flow cytometry showed distinct populations of stage-specific embryonic antigen-4 (SSEA-4), CD49f and CD90 positive cells in the adult human testes. SSEA-4 (+) cells showed high expression levels of SSC-specific genes and high levels of telomerase activity. Extensive colonization of human cells in the mouse testes indicates the presence of highly enriched populations of SSCs in the SSEA-4 (+) sorted cells. All the HNP (+) cells in the mouse testes were positive for germ cell marker dead box mRNA helicase and only half of them were dimly positive for c-kit. In addition, subpopulations of human spermatogonia that colonized mouse testes were positively stained for CD49f, GPR-125, Nanog and Oct-4 indicating the existence of population of cells among human spermatogonia with SSC and pluripotent characteristics.

CONCLUSIONS

This study clearly demonstrates that repopulating human SSCs have phenotypic characteristics of SSEA-4⁺, CD49f⁺, GPR-125⁺and c-Kit ^neg/low. The results have direct implications for enrichment of human spermatogonia for further culture and germ cell differentiation studies.

BACKGROUND

The vitamin D receptor (VDR) is expressed in human spermatozoa, and VDR-knockout mice and vitamin D (VD) deficiency in rodents results in impaired fertility, low sperm counts and a low number of motile spermatozoa. We investigated the role of activated VD (1,25(OH)₂D₃) in human spermatozoa and whether VD serum levels are associated with semen quality.

METHODS

Cross-sectional association study of semen quality and VD serum level in 300 men from the general population, and in vitro studies on spermatozoa from 40 men to investigate the effects of VD on intracellular calcium, sperm motility and acrosome reaction. All men delivered samples for routine semen analysis and blood for measurements of follicle stimulating hormone, Inhibin B, 25-hydroxy-VD, albumin, alkaline phosphatase, calcium and parathyroid hormone (PTH).

RESULTS

In the association study, 44% were VD insufficient (<50 nM), and VD was inversely correlated with PTH (P < 0.0005). VD serum levels correlated positively with sperm motility and progressive motility (P < 0.05), and men with VD deficiency (<25 nM) had a lower proportion of motile (P = 0.027), progressive motile (P = 0.035) and morphologically normal spermatozoa (P = 0.044) compared with men with high VD levels (>75 nM). 1,25(OH)₂D₃ increased intracellular calcium concentration in human spermatozoa through VDR-mediated calcium release from an intracellular calcium storage, increased sperm motility and induced the acrosome reaction in vitro.

CONCLUSIONS

1,25(OH)₂D₃ increased intracellular calcium concentration, sperm motility and induced the acrosome reaction in mature spermatozoa, and VD serum levels were positively associated with sperm motility, suggesting a role for VD in human sperm function.

BACKGROUND

Several studies have examined the relationship between direct antisperm antibody (ASA) levels in semen and pregnancy rate after advanced assisted reproductive technologies (ARTs) but the results have been inconsistent. The aim of our study was to further evaluate the relationship between ASA and pregnancy after IVF or ICSI by systematic review and meta-analysis.

METHODS

We conducted a systematic Medline search of all relevant full papers on direct semen ASA and pregnancy after IVF or ICSI. Three investigators independently reviewed the papers, followed by group discussion to choose the included papers. Meta-analysis was performed to get an odds ratio (OR) for the effect of ASA on pregnancy using IVF or ICSI.

RESULTS

The study identified and analyzed 16 valid studies (10 IVF and 6 ICSI). The study characteristics (including the ASA cutoff values) were heterogeneous. Our meta-analysis revealed that the combined OR for failure to achieve a pregnancy using IVF or ICSI in the presence of positive semen ASA was 1.22 (95% CI: 0.84, 1.77) and 1.00 (95% CI: 0.72, 1.38), respectively. The overall (IVF + ICSI) combined OR was 1.08 (95% CI: 0.85, 1.38).

CONCLUSION

This systematic review and meta-analysis indicate that semen antisperm antibodies are not related to pregnancy rates after IVF or ICSI, suggesting that both forms of ART remain viable options for infertile couples with semen ASA. However, additional, well-designed prospective studies using appropriate ASA cutoff levels are needed to further address this issue.

BACKGROUND

‘Pregnancies of unknown location’ (PULs) include viable and failing intrauterine and extrauterine pregnancies. The aim of this study was to evaluate the role of novel biochemical markers in the prediction of spontaneous resolution of PULs.

METHODS

Serum samples were taken at the first visit to the pregnancy unit for measuring the traditional markers β-hCG and progesterone, and for inhibin A, inhibin pro-αC-related immunoreactivity (inhibin pro-αC-RI) and insulin-like growth factor-binding protein 1 (IGFBP-1). Follow-up was continued until the pregnancy had resolved, the location of the pregnancy and viability was determined or treatment was required. Outcomes were dichotomized into ‘spontaneous resolution’ and ‘other outcome’ categories.

RESULTS

One-hundred and nine cases of PUL were included in the data analysis. Spontaneous resolution occurred in 70% and a further scan was required in 30% to reach a diagnosis. Levels of progesterone and inhibin A were significantly lower (both P < 0.001) and levels of IGFBP-1 significantly higher (P = 0.02) in the pregnancies that spontaneously resolved than in those pregnancies that required further intervention. In decision tree analysis, the novel markers were less useful than progesterone and β-hCG in predicting spontaneously resolving PULs. Inhibin pro-αC-RI and IGFBP-1 were not useful in the prediction of spontaneously resolving PULs. Inhibin A is more predictive than β-hCG alone, but serum progesterone is the best single marker and progesterone and hCG together continues to be the best way of predicting spontaneously resolving PULs.

CONCLUSIONS

These novel biochemical markers are not clinically useful in predicting spontaneously resolving PULs.

BACKGROUND

Proper maternal thyroid function is necessary for a successful pregnancy. In order to identify women who may experience miscarriage due to transient impairment of the pituitary–thyroid axis in early pregnancy, we aimed to investigate the ratio between basal and peak thyroid stimulating hormone (TSH) [following stimulus with thyrotrophin-releasing hormone (TRH)] in euthyroid women with unexplained recurrent miscarriage (RM).

METHODS

We have established a ‘iTSHa index' (TSH increase after TRH adjusted for the levels of basal TSH), determining TSH serum levels at time 0 and 20 min after TRH stimulus in 463 consecutive women attending two antenatal care units for two or more miscarriages occurring within the first 10 weeks of pregnancy.

RESULTS

The mean basal TSH serum levels were higher (P < 0.001) in RM women [2.1 µIU/ml; 95% confidence interval (CI): 2.0–2.2] compared with the controls (1.3 µIU/ml; 95% CI: 1.2–1.4). Establishing serum TSH at an individual level, a large overlap was observed and the receiver operating characteristic curves did not allow us to find an optimal cut-off point with an adequate sensitivity/specificity ratio. Therefore, we suggest a novel statistical model, the ‘iTSHa index' (available on http://www.afar.it/tsh-trh-miscarriage), that is capable of identifying women with RM due to transient thyroid function impairment of the early pregnancy, in particular when baseline serum TSH is less than 1.5 µIU/ml, i.e. well below the conventional upper cut-off indicated as ‘safe' in those who want to conceive.

CONCLUSIONS

A transient impairment of thyroid function in early pregnancy may cause an inadequate adaptation to the increased thyroid requirement and may be implicated in RM. The evaluation of the proposed iTSHa index, if validated in a larger cohort of patients, may provide information useful to identifying a subset of healthy women, without evidence of thyroid dysfunction or autoimmunity and a TSH in the low-normal reference range, who may be at risk of RM.