Decrease in peripheral natural killer cell level during early pregnancy predicts live birth among women with unexplained recurrent pregnancy loss: a prospective cohort study.

BACKGROUND: Previous studies have suggested that trophoblast cells inhibit the proliferation of peripheral natural killer cells and that the level of peripheral natural killer cells decrease in the middle and late pregnancy stage among healthy women. The change in peripheral natural killer cell level during early pregnancy and the relationship between the change in peripheral natural killer cell level and pregnancy outcomes among women with unexplained recurrent pregnancy loss have not been sufficiently explored. OBJECTIVE: This study aimed to characterize the level of prepregnancy peripheral natural killer cells in comparison with those in early pregnancy among women with unexplained recurrent pregnancy loss and to determine if the change in the level of peripheral natural killer cells from prepregnancy to early pregnancy can predict pregnancy outcomes. STUDY DESIGN: In this prospective cohort study, 1758 women with recurrent pregnancy loss were recruited between January 2017 and December 2021 among whom 252 women with unexplained recurrent pregnancy loss had prepregnancy and early pregnancy (4-6 weeks gestation) peripheral natural killer cell measurements. These 252 women were divided into 2 groups, namely those with a lower gestational peripheral natural killer cell level (group 1) when compared with prepregnancy levels and those who did not (group 2). The respective outcomes of these groups in terms of live birth and pregnancy loss were comparatively analyzed using chi-square and Student's t tests. Candidate factors that could influence live birth were selected using the Akaike information criterion. The participates were then randomly divided into training and testing groups. A multivariable logistic regression analysis was performed and a nomogram was created to assess the possibility of live birth. The predictive accuracy was determined by the area under the receiver operating characteristic curve and validated by plotting the predicted probabilities and the observed probabilities. A Hosmer-Lemeshow test was used to assess the goodness of fit. RESULTS: When early gestational peripheral natural killer cell levels were compared with prepregnancy peripheral natural killer cell levels, 61.5% (154) of women had a comparatively lower early-gestational peripheral natural killer cell level and 38.9% (98) of women had an increase or no change in the peripheral natural killer cell level. The live birth rate in group 1 was 89.0% (137/154), which was significantly higher than the rate of 49.0% (48/98) in group 2 (P<.001). A decrease in the peripheral natural killer cell level (odds ratio, 1.36; 95% confidence interval, 1.22-1.55; P<.001) and the anti-Muellerian hormone level (odds ratio, 1.41; 95% confidence interval, 1.14-1.81; P=.003) were important predicting factors for a higher live birth rate. Female body mass index (odds ratio, 0.97; 95% confidence interval, 0.82-1.15; P=.763) and parity (odds ratio, 1.61; 95% confidence interval, 0.71-4.12; P=.287) also were predicting factors. Furthermore, the area under the receiver operating characteristic curve of the model to diagnose of live birth was 0.853 with a sensitivity of 81.6% and a specificity of 78.0% using the training data set. And the Hosmer-Lemeshow test showed that the model was a good fit (p=6.068). CONCLUSION: We report a comparative decrease in the peripheral natural killer cell levels in early gestation when compared with prepregnancy cell levels in more than 60% of women with unexplained recurrent pregnancy loss at 4 to 6 weeks of gestation. When compared with prepregnancy peripheral natural killer cell levels, a decrease in the peripheral natural killer cell level during early pregnancy might be a useful predictor of the live birth rate among women with unexplained recurrent pregnancy loss.

Recurrent miscarriage: green-top guideline nº 17

The purpose of this guideline is to provide guidance on the investigation and care of women and people with recurrent miscarriage.Within this document we use the terms woman and women's health. However, it is important to acknowledge that it is not only women for whom it is necessary to access women's health and reproductive services in order to main-tain their gynaecological health and reproductive wellbeing. Gynaecological and obstetric services and delivery of care must therefore be appropriate, inclusive and sensitive to the needs of those individuals whose gender identity does not align with the sex they were assigned at birth. The term cou-ple is used to describe two individuals trying to conceive, recognising that in some instances these individuals may not be in a relationship. While every effort is made to ensure the RCOG uses inclusive language there are instances where we have been unable to adhere to this, for example where original research is being referenced the language within the publication is used for accuracy.

The use of intrauterine balloon therapy in reproductive medicine and surgery: a guidance for practice.

The use of balloon therapy in obstetric practice especially in postpartum haemorrhage (PPH) is well established and has recently been reviewed. However, little attention has been drawn regarding the use of intrauterine balloon (IUB) in gynaecological practice. This study focuses on the various usage of IUB in gynaecological practice. An electronic literature search through Medline, EMBASE and Clinicaltrial.gov from inception to August 2022 was conducted. The study focuses on the three following areas: (1) Indications: prevention and removal of intrauterine adhesions, management of ectopic pregnancy, facilitation of endoscopic surgery and other clinical usages; (2) Practical aspects of balloon therapy including ultrasound guidance, choice of balloon, inflation volume, duration of balloon therapy; and (3) Potential complications including pain, infection, uterine rupture and how they can be avoided. IUB therapy is a simple, inexpensive and effective method that can be applied in various gynaecological conditions ranging from IUA to intrauterine haemorrhage. Complications are rare, but in most cases can be avoided with correct use.

Adjuvants to prevent reformation of adhesions following adhesiolysis for Asherman syndrome: a systematic review and meta-analysis.

Two international guidelines published on the management of Asherman syndrome (AS) have made recommendations on various adjuvant methods to prevent intrauterine reformation. Nevertheless, the effectiveness of these methods when used in primary or secondary prevention settings is different. Our aim is to assess the effectiveness of various adjuvant methods for the secondary prevention of intrauterine adhesions (IUAs). Articles were considered eligible if they included subjects with AS before surgery and compared a chosen method with either a control or a comparison group (using another method). The primary outcome was the IUA reformation rate at follow-up hysteroscopy. A total of 29 studies [15 randomised controlled trials (RCTs) and 14 cohort studies] were included. Adhesion reformation with various methods to prevented IUA reformation when compared with controls were: second-look hysteroscopy: [risk ratio (RR): 0.21, 95% confidence interval (CI): 0.05-0.90 (p = 0.02)]; intrauterine contraceptive device: RR: 0.64, 95% CI: 0.36-1.12 (p = 0.12); continuous intrauterine balloon: RR: 0.18, 95% CI: 0.05-0.68 (p = 0.01); intermittent intrauterine balloon: RR: 0.50, 95% CI: 0.31-0.80 (p = 0.004); anti-adhesion gel: RR: 0.80, 95% CI: 0.58-1.10 (p = 0.17); amnion graft: RR: 0.63, 95% CI: 0.44-0.91 (p = 0.01).

Does non-cavity distorting intramural fibroid affect endometrium around the time of embryo implantation?

The effect of the intramural fibroids not distorting the cavity remains controversial on implantation and pregnancy. The aim of this study was to examine the impact of non-cavity distorting intramural fibroids on endometrium. Fifty-six women with non-cavity distorting intramural fibroid were recruited in this study. Paired endometrial specimens, one from beneath the fibroid (ipsilateral endometrium) and the other from the opposite side of uterine cavity, away from the fibroid (contralateral endometrium) were obtained 7-9 days after the luteinizing hormone surge in a natural cycle. Histological dating, Mucin1 and Glycodelin expression and uterine natural killer (uNK) cell density were compared between the paired samples. The median (IQR) H-score of Mucin1 staining in the ipsilateral luminal epithelium was 210% (142-230%), which was significantly (p < 0.05) higher than that of the contralateral luminal endometrium (157%, IQR 114-176%). There was no significant difference in Mucin1 expression in the glandular epithelium. There was no significant difference in Glycodelin expression in luminal and glandular epithelium, uNK cells density or histological dating results between the paired endometrial samples. In conclusion, it is uncertain whether the altered expression of Mucin1 in luminal epithelium alone may have impact on implantation when other markers are not changed.

Recurrent MiscarriageGreen-top Guideline No. 17.

In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature. Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C] Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C] Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C] Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D] Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP] Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B] Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C] Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C] Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m2 , smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D] For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B] There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C] Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C] Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A] Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B] Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C].

Blood metal/metalloid concentration of male subjects undergoing IVF/ICSI treatment outcomes: A prospective cohort study.

BACKGROUND: Previous epidemiology studies reported that heavy metal/metalloid exposure is associated with the impairment of semen quality. However, it is still not clear whether the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment outcome will be affected after the heavy metal/metalloid exposure of the male partners. METHODS: A prospective cohort study with a 2-year followed-up was conducted in a tertiary IVF center. A total of 111 couples undergoing IVF/ICSI treatment were initially recruited from November 2015 to November 2016. Male blood concentrations of heavy metal/metalloid including Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Cd, Hg, and Pb were measured by inductively coupled plasma mass spectrometry, and the lab and pregnancy outcome data were followed up. The associations between male blood heavy metal/metalloid concentration and the clinical outcomes were analyzed by Poisson regression analysis. RESULTS: Our results showed that none of the heavy metal/metalloid of male partners we investigated are significantly associated with the oocyte fertilization and good embryo (P ≥ 0.05); however, antral follicle count (AFC) was a protective factor for the oocyte fertilization (RR: 1.07, 95 % CI: 1.04-1.10). The blood Fe concentration of the male partner was positively associated (P < 0.05) with pregnancy in the first fresh cycle (RR:170.93, 95 % CI: 4.13-7082.04), cumulative pregnancy (RR: 23.61, 95 % CI: 3.25-171.64) and cumulative live birth (RR: 36.42, 95 % CI: 1.21-1092.54). In the first frozen embryo cycles, pregnancy was significantly associated (P < 0.05) with the blood Mn (RR: 0.01, 95 % CI:0.00-0.11) and Se concentration (RR: 0.01, 95 % CI:8.25 E-5-0.47) and female age (RR: 0.86, 95 % CI:0.75-0.99); live birth was significantly associated (P < 0.05) with the blood Mn concentration (RR: 0.00, 95 % CI: 1.14E-7-0.51). CONCLUSIONS: Our results suggested that the higher male blood Fe concentration was positively associated with pregnancy in the fresh embryo transfer cycle, cumulative pregnancy, and cumulative live birth, whereas the higher male blood Mn and Se concentration were associated with lower chance of pregnancy and live birth in the frozen embryo transfer cycle. However, the underline mechanism of this finding still needs further investigation.

Value of 2D ultrasonography in the diagnosis and evaluation of intrauterine adhesions - a prospective study.

RESEARCH QUESTION: What is the value of 2D ultrasonography in the diagnosis and assessment of intrauterine adhesions (IUA)? DESIGN: This was a prospective study conducted at a hysteroscopy centre. RESULTS: Of a total of 600 subjects recruited, 41 dropped out and 559 were finally enrolled and analysed. The observed 2D ultrasonography features, in decreasing order of frequency, were 'irregular endometrium' (37.9%), 'broken endometrial echo' (23.4%), 'thin endometrium' (13.7%), 'loss of endometrial echo' (13.1%,), 'hyperechoic focus' (12.5%) and 'fluid in the cavity' (8.8%). The sensitivity of individual ultrasound features ranged from 8.8% to 37.9%, whereas the specificity of individual ultrasound features ranged from 78.9% to 100%. When all the six ultrasound features were considered together, the sensitivity and specificity were 71.7% and 66.2% respectively. The sensitivity, specificity and accuracy of ultrasound diagnosis in the mid-proliferative phase, peri-ovulatory phase and mid-luteal phase did not appear to be significantly different statistically, although the results in the mid-proliferative phase appeared to be consistently higher than those in the mid-luteal phase. In women confirmed to have IUA, the likelihood of the adhesions being severe in nature in the presence of zero, one, two or three or more ultrasound features was 8.7%, 23.0%, 40.2% and 80.5%, respectively (P < 0.001). CONCLUSIONS: The findings in this study support the notions that ultrasonography examination in women suspected to have IUA cannot replace hysteroscopy in the diagnosis of the condition. However, it does provide useful clinical information regarding severity and could help in the planning of hysteroscopy to optimize management.

Female Genital Tuberculosis: Clinical Presentation, Current Diagnosis, and Treatment.

Female genital tuberculosis is a disease caused by Mycobacterium tuberculosis infection in the female reproductive tract. The disease burden among women leads to infertility is significant, especially in developing countries. The bacteria can spread from the lung into the reproductive organ through lymphatic or hematogenous. Many patients present with atypical symptoms, which mimic other gynecological conditions. Several investigations are needed to establish the diagnosis. Almost all cases of genital TB affect the fallopian tube and cause infertility in patients and endometrial involvement. Current treatment still relies on antituberculosis therapy with a combination of tubal surgery. The present review describes the epidemiological data, clinical presentation, diagnosis, and currently available treatment to cure the disease and for in vitro fertilization.

A prospective study comparing the inflammation-related cytokine and chemokine profile from the day of blastocyst transfer to 7 weeks of gestation between pregnancies that did or did not result in a miscarriage.

The dynamics of maternal immunomodulation is essential in early pregnancy. In our previous study, successful implantation is characterized by a transient increase of pro-inflammatory cytokines followed by a switch to an anti-inflammatory state in peripheral blood around 3-6 days after embryo transfer (ET). In this study, we aimed to extend the time points to compare the cytokine and chemokine profiles between women who did or did not subsequently miscarry. We utilized precisely timed serum samples on the day of ET and 3, 6, 9, 16, 23 and 30 days after ET in women undergoing single blastocyst transfer. Our analysis revealed a significant alteration in cytokine profile after day ET+ 9 between the two groups. Regarding pro-inflammatory cytokine profile, there was a significant increase in IL-17 on days ET+ 16, + 23, and + 30 (50.60 ± 9.97 vs 37.09 ± 3.25, 53.20 ± 8.13 vs 36.51 ± 3.34, 57.06 ± 8.83 vs 33.04 ± 3.11 pg/mL), TNF-α on days ET+ 23 and + 30 (73.90 ± 12.42 vs 50.73 ± 3.55, 74.16 ± 12.46 vs 46.59 ± 3.21 pg/mL), IFN-γ on day ET+ 30 (69.52 ± 13.19 vs 42.28 ± 7.76 pg/mL) in women who miscarried compared to women who had a live birth. In contrast, the concentrations of anti-inflammatory cytokines IL-10 on days ET+ 23 and + 30 (26.23 ± 2.11 vs 38.30 ± 4.64, 23.77 ± 2.06 vs 39.16 ± 4.99 pg/mL) and TGF-ß1 on day ET+ 30 (20.30 ± 1.25 vs 23.81 ± 0.88 ng/mL) were significantly decreased in women who miscarried compared to women who had a live birth. While for the chemokine profile, there was no significant alteration observed between the two groups across all the time points. These findings suggest that a sustained anti-inflammatory milieu is concomitant with the maintenance of early pregnancy, while the remarkable pro-inflammatory shift as early as day ET+ 16 in women who subsequently miscarried was observed before the diagnosis of miscarriage.

The efficacy of auto-cross-linked hyaluronic acid gel in addition to oestradiol and intrauterine balloon insertion in the prevention of adhesion reformation after hysteroscopic adhesiolysis.

RESEARCH QUESTION: What is the efficacy of auto-cross-linked hyaluronic acid gel use in preventing adhesion reformation after intrauterine adhesiolysis? DESIGN: This was a single-centre, double-blind randomized controlled trial. RESULTS: In total 171 participants successfully completed the study (84 in the treatment group and 87 in the control group). There was no significant difference in pre-operative variables between the two groups. The primary outcome measure was the adhesion reformation rate at second-look and third-look hysteroscopy. At second-look hysteroscopy, there was no significant difference in adhesion recurrence rate between the treatment group (20.2%, 17/84) and the control group (23.0%, 20/87; P = 0.662). At third-look hysteroscopy, there was also no significant difference in adhesion recurrence rate between the treatment group (9.5%, 8/84) and the control group (11.5%, 10/87; P = 0.675). The secondary outcome measure was the median American Fertility Society (AFS) score, which was not significantly different at second-look hysteroscopy 4 weeks after surgery between the treatment group (0, range 0-4.0) and the control group (0, range 0-4.0; P = 0.475), and at third-look hysteroscopy 8 weeks after surgery between the treatment group (0, range 0-3.5) and the control group (0, range 0-4.0; P = 0.965). Regarding the menstrual flow improvement rate 3 months post-operatively, there was no significant difference between the treatment and control groups (67.9% versus 64.4%; P = 0.630). CONCLUSIONS: The application of auto-cross-linked hyaluronic acid gel does not seem to reduce the incidence and severity of intrauterine adhesion recurrence or affect the menstrual pattern after hysteroscopic removal of mild to moderate intrauterine adhesions.

Female urogenital chlamydia: Epidemiology, chlamydia on pregnancy, current diagnosis, and treatment.

Female urogenital chlamydia is a disease caused by Chlamydia trachomatis infection in the female urogenital tract. It is a common bacterial sexually transmitted disease. The bacteria is transmitted through sexual contact with an infected partner or from mother to newborn during vaginal delivery. The prevalence varies among studies and the number is possibly higher due to the lack of massive screening. Many patients were asymptomatic and still be able to transmit the disease. The undiagnosed and untreated disease could cause pelvic inflammatory disease, which leads to infertility, ectopic pregnancy, and chronic pelvic pain. The prevalence among pregnant women is similar to non-pregnant women, therefore chlamydia screening in pregnant women is highly recommended. The nucleic acid amplification test is the most reliable method for the diagnosis due to high sensitivity. The current treatment is given by prescribing antibiotics.

In vitro rescue immature oocytes - a literature review.

Immature oocytes retrieved from in vitro fertilization (IVF) and clinical in vitro maturation (IVM) is a common problem, especially in patients with advanced age, poor ovarian response (POR), or polycystic ovary syndrome (PCOS). Considering there is no common name to describe this group of oocytes, we suggest naming all of immature oocytes retrieved from IVF and clinical IVM cycles as 'Medical Unusable Oocytes' (MUO) as none of them will be used for subsequent treatment and will eventually be discarded. Scientists attempt to improve the clinical utilization rate of MUO instead of discarding them. Rescue IVM and mitochondria supplementation may be available approaches to mature MUO. We propose a specific definition of rescue IVM, namely the cultivation and maturation of immature oocytes in vitro collected from IVF cycles with human chorionic gonadotropin (hCG) trigger. Rescue IVM is usually mixed up with clinical IVM. Clarification of the differences between rescue IVM and clinical IVM is necessary. This manuscript aims to clarify the rather confusing IVM procedures and review existing methods of improving rescue IVM, currently available information on the success rate, and explore the future possibility of rescue IVM serving as a promising tool in reproductive medicine.

The identification of endometrial immune cell densities and clustering analysis in the mid-luteal phase as predictor for pregnancy outcomes after IVF-ET treatment.

Changes in endometrial immune cell density has been reported to be associated with reproductive failure. The prognostic value of endometrial immune cell density measurement remains uncertain. We aimed to investigate the prognostic value of endometrial immune cells measurement on pregnancy outcome after IVF in women. In this prospective study, one hundred twenty-eight women underwent endometrial sampling in a natural cycle preceding single frozen-thawed embryo transfer (ET). Endometrial biopsy was obtained precisely 7 days after luteinizing hormone surge (LH + 7). Multiplex immunohistochemical method was employed to simultaneously stain the endometrium samples with a panel of human antibodies against CD56 for uterine natural killer (uNK) cells, CD3 and CD8 for T cell, CD3 for pan T cells and CD68 for macrophages. The density of the various immune cells and the clustering levels between them were measured. ET was performed at the blastocyst stage. Women who did not conceive had a significantly higher density of uNK cells and higher clustering level between uNK cells-and-macrophages than women who did conceive. In accordance, the prognostic value of uNK measurement on pregnancy outcome was significantly improved when combined with uNK-to-macrophage clustering analysis simultaneously. Taken together, our results suggested that uNK cells density and clustering level between uNK cells-and macrophages may be a promising predictor for successful implantation after IVF-ET.

The association of chronic endometritis with mid-trimester loss due to cervical incompetence and the outcome of laparoscopic cervical cerclage.

PURPOSE: To examine the association of chronic endometritis (CE) with cervical incompetence (CI) in Chinese women with mid-trimester loss, and the impact of the presence of CE on the outcome of laparoscopic cervical cerclage (LCC). METHODS: This retrospective cohort study included a study group of 293 women with mid-trimester loss due to CI (group I) and a comparison group of 332 women with recurrent first-trimester miscarriage (group II). Immunohistochemical study using CD138 epitope for the diagnosis of CE was completed in all subjects. Pre-conception LCC was undertaken in 247 women in the study group (group I). The study was approved by Institutional Review Board (IRB) (number 2015FXHEC-KY005). RESULTS: The prevalence of CE in group I was 42%, significantly (P < 0.001) higher than that of 23.5% in group II. Among 247 women in group I, there were no significant difference in mid-trimester loss rate, preterm delivery rate and term delivery rate in women with and without CE (2.2, 12.0, 85.8% vs. 1.8, 10.1, 88.1% respectively) and between women with CE treated and not treated with antibiotics prior to conception (2.3, 9.3, 88.4% vs. 2.0, 14.3, 83.7% respectively). CONCLUSIONS: Mid-trimester loss due to cervical incompetence is associated with chronic endometritis; However, the presence or not of CE and whether it was treated with antibiotics prior to conception did not appear to significantly influence the obstetric outcomes of women with CI after LCC.

The number of previous failed embryo transfer cycles is an independent factor affecting implantation rate in women undergoing IVF/ICSI treatment: A retrospective cohort study.

ABSTRACT: The implantation rate (IR) in assisted reproductive technologies such as in vitro fertilization (IVF) and intracytoplasmic sperm injection is affected by many different factors such as age, quality of embryo, and stage of embryo development. This study aimed to investigate to what extent the number of previous failed embryo transfer cycles is an independent factor affecting IR.This was a single-center, retrospective cohort study of a consecutive series of 6376 day-3 embryo transfer (ET) cycles following IVF between January 2012 and August 2018. None of the subjects underwent endometrial scratch/injury prior to the treatment cycle, or received intravenous immunoglobulin, steroid, dehydroepiandrosterone, intralipid or heparin during the treatment with the aim of improving implantation rates.Multiple regression analysis showed that the 3 most important independent factors affecting the IR, in decreasing of importance: age, frozen or fresh embryo transfer and the number of previous ET cycles. Having controlled for 2 of the more important confounding variables including maternal age and the type of embryo, the IR in women who had 0, 1, 2, and 3 or more previous failed ET cycles were 45.8%, 35.9%, 31.2%, 21.0%, respectively (P < .001).Repeated implantation failure is a significant independent factor affecting the IR. The number of previous failed ET cycles should be considered in counselling women regarding the prognosis of a further IVF-ET treatment cycle.

Associations between blood metal/ metalloid concentration and human semen quality and sperm function: A cross-sectional study in Hong Kong.

BACKGROUND: The association between metal/metalloid exposure on human sperm quality is still inconclusive. There is a lack of data on the effect of metal/metalloid on sperm function. METHODS: The aim of this study was to clarify the association between blood metal/metalloid concentration and traditional and functional sperm parameters, the blood concentration of Pb, Hg, Cd, As, Ni, Mo, Zn, Cu, Se, Fe, Mg, Cr and Ca of 288 men in Hong Kong were assessed by inductively coupled plasma-mass spectrometry, and sperm parameters including sperm concentration, motility, morphology, vitality, total sperm count, total motile sperm count, sperm DNA fragmentation and sperm acrosome reaction were measured. Demographic and lifestyle questionnaires were also provided for all participants. Multivariable linear regression analysis was performed to test the association between blood metal/ metalloid concentration and semen parameters after adjusting for relevant confounding variables. RESULTS: The results showed that moderate to high level of blood Pb concentration (>27.19 µg/L) appeared to be negatively associated with sperm morphology (P < 0.05); high level of blood Cd concentration (>1.44 µg/L) was negatively associated with sperm acrosome reaction (P < 0.05); Mo was positively associated with semen volume (P < 0.05), however, high level of blood Mo concentration (>13.52 µg/L) was negatively associated with sperm vitality (P < 0.05); high level of blood Zn concentration (>6.20 mg/L) was positively associated with sperm vitality (P < 0.05); moderate level of blood Fe concentration (526.89-566.63 mg/L) was positively associated with sperm acrosome reaction (P < 0.05); moderate level of blood Ca concentration (55.92-66.10 mg/L) was positively associated with semen volume (P < 0.05); however, lower level of blood Ca concentration (45.90-55.92 mg/L) was negatively associated with sperm morphology (P < 0.05). CONCLUSIONS: Our results suggested that the sperm function could be affected by blood Cd and Fe concentration and traditional sperm parameters could be affected by blood concentration of Mo, Zn, Pb and Ca.

Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: a prospective randomized control trial.

OBJECTIVE: To compare the rates of negative test results for chronic endometritis (CE) between subjects who did and did not receive antibiotic treatment. DESIGN: Prospective, single-blind randomized controlled trial. SETTING: Tertiary hysteroscopic center in a university teaching hospital. PATIENT(S): A total of 132 women with CE confirmed with immunohistochemical study with CD138 epitope. INTERVENTION(S): Women randomized to antibiotic therapy received oral levofloxacin 500 mg and tinidazole 1,000 mg daily for 14 days. Women randomized to the control group did not receive any treatment. A repeated endometrial biopsy was performed 4 to 8 weeks after the initial biopsy to determine whether CE was still present. MAIN OUTCOME MEASURE(S): The rate of negative test results for CE (from positive to negative). RESULT(S): The CE rate of negative test results in the treatment group (89.3%) after one course of antibiotic treatment was significantly higher than that in the control group (12.7%). Among subjects who attempted pregnancy, there was no significant difference in ongoing pregnancy rates and miscarriage rates between the treatment arm (43.2%, 5.4%) and the control arm (25.7%, 14.3%). Among subjects randomized, there was also no significant difference in ongoing pregnancy rates and miscarriage rates between the treatment arm (27.1%, 3.4%) and the control arm (16.4%, 9.1%). CONCLUSION: A course of broad-spectrum oral antibiotic therapy for 14 days is effective in the treatment of CE in >89.8% of cases. However, it is not yet clear whether treatment improved pregnancy outcomes. CLINICAL TRIAL IDENTIFICATION NUMBER: NCT02648698.