It is known that infertility affects emotional well-being, satisfaction with life and self-esteem and that failed assisted reproductive technology (ART) treatment is associated with diminished life satisfaction, reduced self-confidence and substantial psychological distress. Investigations of whether these persist when treatment results in a pregnancy and live birth have been undertaken.
A systematic search for English-language research articles on psychological and social aspects of pregnancy, childbirth and the first post-partum year after ART conception.
Of 466 retrieved papers, 46 met inclusion criteria. These reported data from 28 studies. There is consistent evidence that marital satisfaction, emotional well-being and self-regard in pregnancy, attachment to the fetus and parent–infant relationship in ART groups are similar to comparison groups. Anxiety about the survival of the fetus and early parenting difficulties appear to be higher and post-natal self-confidence lower. Evidence about adjustment to pregnancy and parenthood and the experience of childbirth is inconclusive and reports of parental perceptions of infant temperament and behaviour are contradictory. Between-study methodological differences may explain the lack of consistency in findings of the influence of infertility and ART on some aspects of the transition to parenthood.
Overall, this body of evidence is best described as emergent. It is possible that in pregnancy after ART, parenthood might be idealized and this might then hinder adjustment and the development of a confident parental identity.
The prevalence of congenital uterine anomalies in women with reproductive failure remains unclear, largely due to methodological bias. The aim of this review is to assess the diagnostic accuracy of different methodologies and estimate the prevalence of congenital uterine anomalies in women with infertility and recurrent miscarriage (RM).
Studies from 1950 to 2007 were identified through a MEDLINE search; all relevant references were further reviewed.
The most accurate diagnostic procedures are combined hysteroscopy and laparoscopy, sonohysterography (SHG) and possibly three-dimensional ultrasound (3D US). Two-dimensional ultrasound (2D US) and hysterosalpingography (HSG) are less accurate and are thus inadequate for diagnostic purposes. Preliminary studies (n = 24) suggest magnetic resonance imaging (MRI) is a relatively sensitive tool. A critical analysis of studies suggests that the prevalence of congenital uterine anomalies is ~6.7% [95% confidence interval (CI), 6.0–7.4] in the general population, ~7.3% (95% CI, 6.7–7.9) in the infertile population and ~16.7% (95% CI, 14.8–18.6) in the RM population. The arcuate uterus is the commonest anomaly in the general and RM population. In contrast, the septate uterus is the commonest anomaly in the infertile population, suggesting a possible association.
Women with RM have a high prevalence of congenital uterine anomalies and should be thoroughly investigated. HSG and/or 2D US can be used as an initial screening tool. Combined hysteroscopy and laparoscopy, SHG and 3D US can be used for a definitive diagnosis. The accuracy and practicality of MRI remains unclear.
The complexity of fertilization failure during assisted reproductive technologies (ART) is often under-appreciated, as this failure can occur at any number of essential mechanistic and cellular events. Importantly, successful fertilization is heavily dependent upon inherent qualities of the oocytes, and thus reliant upon fidelity of oocyte maturation.
Pubmed and medline were searched up to April 2008 for papers on oocyte fertilization and its mechanistic components. References to clinical/human studies were selected wherever possible.
Successful oocyte maturation cannot simply be determined via visual assessment of polar body extrusion, but rather entails coordination of numerous cytoplasmic processes not readily observed. Proper regulation of intra-oocyte signaling cascades is crucial for sufficient production and storage of carbohydrates and proteins, successful relocation of organelles and regulation of metabolic pathways required for an apparently mature metaphase II oocyte to complete subsequent fertilization events; such as cumulus penetration, sperm/oocyte binding, fusion, oocyte activation, sperm processing and pronuclear (PN) formation. Regulation of oocyte maturation begins during oocyte growth and is intimately connected with events influencing folliculogenesis. Therefore, the oocyte is subject to a multitude of potential effector impacting fertilization potential and developmental competence long before encountering the artificial environment of the IVF laboratory.
Although meticulous care and continued research is essential for future improvement, failure to fertilize and properly form PN following clinical ART is likely to be dependent on historical events in oocyte maturation, not easily explained or prevented through simple modification of contemporary laboratory protocols.
Genetic variation contributes to the risk of developing endometriosis. This review summarizes gene mapping studies in endometriosis and the prospects of finding gene pathways contributing to disease using the latest genome-wide strategies.
To identify candidate-gene association studies of endometriosis, a systematic literature search was conducted in PubMed of publications up to 1 April 2008, using the search terms ‘endometriosis’ plus ‘allele’ or ‘polymorphism’ or ‘gene’. Papers included were those with information on both case and control selection, showed allelic and/or genotypic results for named germ-line polymorphisms and were published in the English language.
Genetic variants in 76 genes have been examined for association, but none shows convincing evidence of replication in multiple studies. There is evidence for genetic linkage to chromosomes 7 and 10, but the genes (or variants) in these regions contributing to disease risk have yet to be identified. Genome-wide association is a powerful method that has been successful in locating genetic variants contributing to a range of common diseases. Several groups are planning these studies in endometriosis. For this to be successful, the endometriosis research community must work together to genotype sufficient cases, using clearly defined disease classifications, and conduct the necessary replication studies in several thousands of cases and controls.
Genes with convincing evidence for association with endometriosis are likely to be identified in large genome-wide studies. This will provide a starting point for functional and biological studies to develop better diagnosis and treatment for this debilitating disease.
The identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome (PCOS). Since an altered response to ovarian stimulation is also a characteristic of the disease, further knowledge about its aetiology could help in defining the parameters that determine the response of an individual to ovarian stimulation.
PubMed and EMBASE databases were systematically searched for gene association studies published until the end of August 2007, using search criteria relevant to PCOS and ovarian response to stimulation. Data from additional papers identified through hand searches were also included; 139 publications were reviewed.
Several genes involved in ovarian function and metabolism are associated with increased susceptibility to PCOS, but none is strong enough to correlate alone with susceptibility to the disease, or response to therapy. A single-nucleotide polymorphism in exon 10 of the FSH receptor (FSHR) gene, FSHR p.N680S, was consistently identified as having a significant association with ovarian response to FSH.
No consistent association between gene polymorphism and PCOS could be identified. The FSHR gene may play a significant role in the success of ovarian stimulation, and can be used as a marker to predict differences in FSHR function and ovarian response to FSH. Genotyping the FSHR p.N680S polymorphism may provide a means of identifying a population of poor responders before in vitro fertilization procedures are initiated.
Histamine has been assumed to contribute to embryo–uterine interactions due to its vasoactive, differentiation and growth-promoting properties. However, its exact functions in pregnancy are unclear. The histamine-degrading enzyme diamine oxidase (DAO) is produced in high amounts by the placenta and has been supposed to act as a metabolic barrier to prevent excessive entry of bioactive histamine from the placenta into the maternal or fetal circulation.
The literature available on PubMed published in English between 1910 and 2008 has been searched using the isolated and combined key words histamine, diamine oxidase, pregnancy, placenta, endometrium, miscarriage, implantation, pre-eclampsia, intrauterine growth retardation, diabetes and embryonic histamine-releasing factor (EHRF).
High expression of the histamine-producing enzyme histidine decarboxylase in the placenta, histamine receptors at the feto–maternal interface and the existence of an EHRF suggest a physiological role of histamine during gestation. The balance between histamine and DAO seems to be crucial for an uncomplicated course of pregnancy. Reduced DAO activities have been found in multiple heterogeneous complications of pregnancy such as diabetes, threatened and missed abortion and trophoblastic disorders. Whether women with histamine intolerance suffer from more complicated pregnancies and higher abortion rates due to impaired DAO activities and if low DAO levels or genetic modifications in the DAO gene might therefore represent a prognostic factor for a higher risk of abortion, has not been investigated yet.
Low activities of the histamine-degrading enzyme DAO might indicate high-risk pregnancies, although high intra- and interindividual variations limit its value as a screening tool.
Despite extensive studies of the developmental consequences of increased glucocorticoid exposure in mid- to late pregnancy, relatively little is known regarding the significance of glucocorticoids in early pregnancy. The objective of this review was to consider potential roles for this family of corticosteroids that might relate to early pregnancy.
Although this is a narrative review, 249 source articles addressing potential effects of glucocorticoids on aspects of early pregnancy and development (published between 1997 and 2007) were identified using a systematic literature search. Additional articles (115) were identified if cited by the primary reference articles identified in the systematic phase of the review.
Much of the evidence to implicate glucocorticoids in early pregnancy comes from studies of steroid receptors and the 11β-hydroxysteroid dehydrogenase enzymes, which modulate cortisol action in the endometrium/decidua, trophoblast, placenta and embryo/fetus. The evidence reviewed suggests that in early pregnancy the actions of glucocorticoids are balanced between positive effects that would promote pregnancy (e.g. stimulation of hCG secretion, suppression of uterine natural killer cells, and promotion of trophoblast growth/invasion) versus adverse effects that would be expected to compromise the pregnancy (e.g. inhibition of cytokine-prostaglandin signalling, restriction of trophoblast invasion following up-regulation of plasminogen activation inhibitor-1, induction of apoptosis, and inhibition of embryonic and placental growth).
Glucocorticoids exert many actions that could impact both negatively and positively on key aspects of early pregnancy. These steroids may also be implicated in obstetric complications, including intra-uterine growth restriction, pre-term labour, pre-eclampsia and chorio-aminionitis.
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are two prominent signaling lysophospholipids (LPs) exerting their functions through a group of G protein-coupled receptors (GPCRs). This review covers current knowledge of the LP signaling in the function and pathology of the reproductive system.
PubMed was searched up to May 2008 for papers on lysophospholipids/LPA/S1P/LPC/SPC in combination with each part of the reproductive system, such as testis/ovary/uterus.
LPA and SIP are found in significant amounts in serum and other biological fluids. To date, 10 LP receptors have been identified, including LPA1–5 and S1P1–5. In vitro and in vivo studies from the past three decades have demonstrated or suggested the physiological functions of LP signaling in reproduction, such as spermatogenesis, male sexual function, ovarian function, fertilization, early embryo development, embryo spacing, implantation, decidualization, pregnancy maintenance and parturition, as well as pathological roles in ovary, cervix, mammary gland and prostate cancers.
Receptor knock-out and other studies indicate tissue-specific and receptor-specific functions of LP signaling in reproduction. More comprehensive studies are required to define mechanisms of LP signaling and explore the potential use as a therapeutic target.