1. Human Reproduction

Category Archives: Human Reproduction

Potential reproductive toxicity of Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage

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BACKGROUND

Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth.

METHODS

Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1x, 2x, 3x and up to 6x clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied.

RESULTS

In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats.

CONCLUSIONS

Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

The prevalence and impact of fibroids and their treatment on the outcome of pregnancy in women with recurrent miscarriage

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BACKGROUND

Although uterine fibroids have been associated with spontaneous miscarriage, to our knowledge there have been no studies in the literature assessing their role in the recurrent miscarriage (RM) population. The aims of this study are to examine the impact of different types of fibroids on the pregnancy outcome of women with RM and to investigate to what extent resection of fibroids distorting the uterine cavity affects the outcome of a future pregnancy.

METHODS

The study analysed retrospective and prospective data from a large tertiary referral RM clinic. Couples were investigated as per an established protocol. Fibroids were diagnosed using combined transvaginal ultrasound and hysterosalpingography. Fibroids distorting the uterine cavity were resected via hysteroscopy. Two study groups were subsequently examined: women with cavity-distorting fibroids who underwent surgery (n =25) and women with fibroids not distorting the cavity who did not undergo any intervention (n =54). The latter was compared with a control group of women with unexplained RM (n =285).

RESULTS

The prevalence of fibroids was found to be 8.2% (79/966). In total, 264 pregnancies of women with fibroids and 936 pregnancies of women with unexplained RM were analysed. Women with intracavitary distortion and undergoing myomectomy significantly reduced their mid-trimester miscarriage rates in subsequent pregnancies from 21.7 to 0% (P< 0.01). This translated to an increase in the live birth rate from 23.3 to 52.0% (P< 0.05). Women with fibroids not distorting the cavity behaved similarly to women with unexplained RM achieving a 70.4% live birth rate in their subsequent pregnancies without any intervention.

CONCLUSIONS

Fibroids are associated with increased mid-trimester losses amongst women with RM. Resection of fibroids distorting the uterine cavity can eliminate the mid-trimester losses and double the live birth rate in subsequent pregnancies. Women with fibroids not distorting the uterine cavity can achieve high live birth rates without intervention.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Chlamydia trachomatis infection in fertile and subfertile women in Rwanda: prevalence and diagnostic significance of IgG and IgA antibodies testing

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BACKGROUND

In many developing countries, little is known about the prevalence of genital Chlamydia trachomatis infections and complications, such as infertility, thus preventing any policy from being formulated regarding screening for C. trachomatis of patients at risk for infertility. The objective of the present study was to determine the prevalence of C. trachomatis and evaluate the diagnostic utility of serological markers namely anti-C. trachomatis IgG and IgA antibodies in women attending an infertility clinic.

METHODS

Serum and vaginal swab specimens of 303 women presenting with infertility to the infertility clinic of the Kigali University Teaching Hospital and 312 fertile controls who recently delivered were investigated. Two commercial species-specific ELISA were used to determine serum IgG and IgA antibodies to C. trachomatis and vaginal swabs specimens were tested by PCR. Hysterosalpingography (HSG) was performed in subfertile women.

RESULTS

The PCR prevalence of C. trachomatis infection was relatively low and did not differ significantly among subfertile and fertile women (3.3 versus 3.8%). Similarly, no significant differences in overall prevalence rates of C. trachomatis IgG and IgA among both groups were observed. The only factor associated with C. trachomatis infection in our study population was age <25 years. The seroprevalence of IgG in both assays (86.4% for ANILabsystems and 90.9% for Vircell) was significantly higher in the group of PCR C. trachomatis-positive women compared with that of PCR-negative women. Evidence of tubal pathology identified by HSG was found in 185 patients in the subfertile group (67.8%). All the serological markers measured in this study had very low sensitivities and negative predictive values in predicting tubal pathology. The specificities for ANILabsystems IgG, Vircell IgG, Anilabsystem IgA and positive C. trachomatis DNA to predict tubal pathology were 84, 86, 95 and 98%, respectively, whereas their respective positive predictive values were 73, 76, 81 and 80%.

CONCLUSIONS

The prevalence of C. trachomatis in our study population in Rwanda appears to be low and women aged <25 years are more likely to have genital infection with C. trachomatis. Since serological testing for Chlamydia shows an excellent negative predictive value for lower genital tract infection, specific peptide-based serological assays may be of use for screening in low prevalence settings. Our data suggest that C. trachomatis is not the primary pathogen responsible for tubal pathology in Rwandan women.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Affordable ART: a different perspective

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BACKGROUND

Although ~10% of the population is affected by infertility, the treatment option of in-vitro fertilisation (IVF) remains unaffordable for the majority of infertile couples. We have initiated a lowcost programme incorporating an uncommonly used, but recognized, ovarian stimulation protocol, together with certain costlimiting initiatives in an established assisted reproductive technology (ART) set up.

METHODS

The medical records of women who underwent the lowcost programme were analysed. Clomiphene citrate 50 mg daily was administered from Day 2 of the cycle and continued till the day of hCG trigger, thus preventing the LH surge. Intermittent doses of human menopausal gonadotrophin 150 IU were administered on alternate days from the 5th day onwards. Oocyte retrieval was carried out once at least two follicles of >18 mm were identified. The cycle was monitored by ultrasound only, with embryo transfer being carried out on Day 3. Clinical outcomes were recorded together with an estimation of the direct costs per cycle. Direct cost calculations did not include professional charges or facility costs.

RESULTS

Of 143 women evaluated, 104 women underwent embryo transfer. The live birth rate and clinical pregnancy rate per embryo transfer were 19 and 22%. The live birth rate per initiated cycle was 14% (20/143). The multiple pregnancy rate was 26% with no case of ovarian hyperstimulation syndrome being recorded. The average direct cost per cycle was US$ 675 for IVF and US$ 725 for an ICSI treatment cycle.

CONCLUSIONS

Using this protocol, together with several costcutting measures, we achieved an acceptable live birth rate per transfer of 19% at a reasonable cost. This approach could be used by established ART centres to provide treatment to couples who cannot afford conventional ART.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Ovarian cortex transplantation in the baboon: comparison of four different intra-abdominal transplantation sites

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BACKGROUND

Several sites have been used for ovarian cortex transplantation (OCT) in humans. The present study was designed to evaluate different intra-abdominal transplantation sites in the baboon to gain further knowledge about alternative transplantation sites in a human setting.

METHODS

Autologous fresh OCTs were performed in 12 baboons (Papio anubis). Four different sites were tested: the free portion of the omentum (OMF), the portion of the omentum adjacent to the spleen (OMS), the pouch of Douglas (D) and the pelvic wall on the psoas muscle (PW). Cortex survival, follicle density, cyclicity and hormonal levels were compared between the different sites, 3 and 6 months after transplantation.

RESULTS

Macroscopically, antral follicles were only found in the OMS and OMF locations, which also showed a higher proportion of follicle-containing cortex at light microscopy (OMF 71.4%, OMS 83.3% versus PW 58.8% and D 40%, P< 0.05). Higher densities of primordial [OMF: 3.54 (0–13.18) follicles/grid, OMS: 3.85 (0–8.53), PW: 0 (0–13.25), D 0 (0–1.33), P< 0.05] and primary follicles [OMF: 3.54 (0–18.52), OMS: 3.85 (0–1), PW: 0 (0–4.58), D 0 (0–0.25), P< 0.05] was also found in the omental locations.

CONCLUSIONS

Omental locations provide a better site, in terms of follicle survival, for intra-abdominal OCT in the baboon compared with the pelvic wall and the D.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

The expression of activins, their type II receptors and follistatin in human Fallopian tube during the menstrual cycle and in pseudo-pregnancy

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BACKGROUND

The Fallopian tube (FT) is the site of fertilization and early embryonic development. We have previously reported the expression of activins, their receptors and follistatin by the FT. Here, our aim was to study the expression of tubal activins, their type II receptors and follistatin during the menstrual cycle and following exposure to hCG in vivo.

METHOD

A set of 30 FTs were collected from cycling women (n = 12) at different stages of the cycle (n = 4 in each stage) and pseudo-pregnant women (n = 3) at the time of hysterectomy for benign disease. The pseudo-pregnant women were injected with hCG in the days leading up to hysterectomy, and pseudo-pregnancy was confirmed by the persistence of amenorrhea, the presence of corpus luteum and decidualization of the endometrium. FT specimens were examined using immunohistochemistry and quantitative RT–PCR.

RESULTS

The expression of activin βA- and βB-subunits, activin type IIA and IIB receptors, and follistatin varied throughout the menstrual cycle, being lowest in the follicular phase and highest in the luteal phase. These results were demonstrated at the mRNA and protein level by quantitative RT–PCR and immunohistochemistry (P< 0.05). HCG injection rescued the expression of the candidate molecules from falling to the follicular stage levels but the expression remained lower than in the luteal phase.

CONCLUSIONS

We suggest that activins play a role in tubal physiology and early embryonic development. Additionally, exposure of the tubal epithelium to hCG modulates the expression of tubal activins.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Depression, anxiety and cardiometabolic risk in polycystic ovary syndrome

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BACKGROUND

Polycystic ovary syndrome (PCOS) is associated with psychological and metabolic disturbances. The aim of this study was to determine whether depression, anxiety and reduced health-related quality of life (HRQOL) are more common in women with PCOS and associated with metabolic risk.

METHODS

The study included 226 PCOS patients and 85 BMI-matched healthy control women. All participants completed standardized questionnaires assessing depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory) and both depression and anxiety (Hospital Anxiety and Depression Scale and General Health Questionnaire). Patients also completed a PCOS HRQOL questionnaire. Hirsutism scores, serum androgens and lipids were obtained. All subjects underwent a standard oral glucose tolerance test.

RESULTS

28.6% of PCOS women versus 4.7% of control women had clinical depression scores indicating an 8.1-fold increased risk of depression in PCOS (P < 0.001). Depression and anxiety scores were higher in PCOS women than controls (P < 0.01 for all subscales). Obese PCOS subjects had higher depression scores and rates than non-obese PCOS women (P < 0.05). Depression scores were significantly correlated with insulin resistance and lipid parameters and with the number of components comprising the metabolic syndrome. Menstrual and hirsutism problems were the most serious concerns followed by emotional problems on the HRQOL.

CONCLUSIONS

Depression and anxiety are more common in patients with PCOS compared with healthy women. Depression in PCOS might be associated with obesity and metabolic abnormalities including insulin resistance and dyslipidemia.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Conditional embryo relinquishment: choosing to relinquish embryos for family-building through a Christian embryo ‘adoption’ programme

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BACKGROUND

Currently, there is little evidence about conditional relinquishment of frozen embryos to others for family-building. This paper begins to address this gap by reporting findings from a study that investigated the experiences of couples who chose to relinquish their embryos conditionally through an embryo ‘adoption’ programme.

METHODS

An exploratory qualitative study was conducted between September 2008 and December 2009. Participants were recruited from a Christian embryo ‘adoption’ programme in the USA. Forty-three people (18 couples and 7 wives) participated in in-depth email interviews.

RESULTS

The data show that the following factors contributed to the participants choosing an embryo ‘adoption’ programme: how they conceptualized their embryos; dislike of alternative disposition options available; conceptions of their parental responsibility towards their embryo and a desire to have an ‘open’ relinquishment with (varying) degrees of information-sharing and contact arrangements between themselves and recipient couples.

CONCLUSIONS

This study identifies a diversity of views on embryo relinquishment and some couples’ wishes for elements of conditional relinquishment that are offered by embryo ‘adoption’ programmes. A range of disposition options should be available to enhance choice for those with unused embryos so that they can relinquish in ways that are both morally and practically acceptable to them. The current polarized debate concerning the language of embryo ‘adoption’ detracts attention from the practical considerations of formulating ‘best practice’ in this area. These considerations are better addressed by the use of less politically charged terminology such as ‘conditional relinquishment’.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Developmental assessment of human vitrified-warmed blastocysts based on oxygen consumption

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BACKGROUND

In this study, we aimed to develop a model for embryo selection based on oxygen consumption following cryopreservation, the relationship between the developmental competence of blastocysts and their oxygen consumption was assessed.

METHODS

Oxygen consumption of vitrified-warmed human blastocysts was measured at 0, 1.5, 3, 4.5, 6, 7.5, 9 and 24 h after warming using scanning electrochemical microscopy. On the basis of their developmental stage at 24 h, blastocysts were classified into four groups (hatched, hatching, arrested and degenerated). Moreover, cytochrome c oxidase (CCO) activity in vitrified-warmed blastocysts was assessed at 0 and 24 h.

RESULTS

The oxygen consumption rate of blastocysts just after warming was significantly lower than that of non-vitrified blastocysts (P< 0.05). The oxygen consumption rate of blastocysts was significantly higher in the hatched group than in the arrested and the degenerated groups after 1.5 h (P< 0.05) and than in the hatching group (P< 0.05) at 7.5 and 9 h. Moreover, CCO activity was absent in vitrified-warmed blastocysts at 0 h, but was detected at 24 h.

CONCLUSIONS

The respiratory rate of vitrified blastocysts after warming was significantly lower than non-cryopreserved blastocysts. Oxygen consumption of blastocysts with high developmental potential was restored earlier than that of blastocysts with low developmental potential. The results of this study suggest that it is possible to select vitrified-warmed blastocysts with high developmental potential based on their respiratory activity.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Cytomegalovirus sero positivity dramatically alters the maternal CD8+ T cell repertoire and leads to the accumulation of highly differentiated memory cells during human pregnancy

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BACKGROUND

Human pregnancy offers an immunological challenge for the immunocompetent women accommodating an allogenic fetus, while continuing to combat potentially infectious disease. Cytomegalovirus (CMV) infects the majority of the human population and establishes lifelong persistence, which can lead to the oligoclonal expansion of differentiated T cells. Primary CMV infection and, less commonly, secondary infection during pregnancy can cause fetal disease and morbidity. The balance between maternal immune competence and viral pathogenicity is thus delicately poised. Our objective was to investigate the influence of CMV serostatus on maternal CD8+ T-cell phenotype and cytokine profile in an apparently healthy cohort of pregnant women. Furthermore, we assessed if CMV serostatus modulated changes in CD8 T cells during gestation.

METHODS

CD8+ T-cell phenotype was investigated in 87 pregnant women with samples obtained both during pregnancy [CMV immunoglobulin G (IgG) + n = 39, CMV IgG– n = 21] and in the early post-natal period (IgG+ n = 16, IgG– n = 11). Multiparameter flow cytometry was used to study T-cell phenotype and HLA-peptide tetramers identified CD8 T cells specific for CMV. Levels of 26 plasma cytokines, chemokines and chemokine receptors were assessed in a separate cohort of 20 women (IgG+ n = 10, IgG– n = 10) followed longitudinally during and after pregnancy.

RESULTS

CMV seropositivity profoundly influenced the T cell repertoire and its dynamics during pregnancy. Naïve CD8+ T-cells (CCR7+CD45RA+) were reduced by 50% in CMV-seropositive women. The proportion of CD45RA effector cells was not increased in CMV-seropositive donors, although this population was more highly differentiated with reduced CD27 and CD28. However, there was a doubling in the proportion of CD45RA+ revertant memory cells (CCR7–CD45RA+) in seropositive donors. Moreover, seropositive women during late pregnancy demonstrated an accumulation of highly differentiated CMV-specific T-cells. T-cell activation independent of CMV was also seen in late pregnancy. No CMV-related changes in plasma cytokines, chemokines or their receptors were observed.

CONCLUSIONS

Thus, CMV serostatus is a crucial consideration in studies of T cell memory and differentiation during pregnancy. The reduction in maternal naïve T cells in CMV-seropositive donors could have implications for the maternal response to infections during pregnancy. These findings shed light on the delicate balance between host, fetus and chronic infection during healthy pregnancy and will inform studies in relation to the importance of CMV on maternal and fetal health.

Source:
http://humrep.oxfordjournals.org/rss/current.xml


  1. Human Reproduction