The Association Between Elevated Progesterone Level on Day of hCG Trigger and Live Birth Rates in ART Cycles: A Single Centre Observational Study.

BACKGROUND: The advent of ovarian stimulation within an in vitro fertilization (IVF) cycle has resulted in modifying the physiology of stimulated cycles and has helped optimize pregnancy outcomes. In this regard, the importance of progesterone (P4) elevation at time of human chorionic gonadotrophin (hCG) administration within an IVF cycle has been studied over several decades. Our study aimed to evaluate the association of P4 levels at time of hCG trigger with live birth rate (LBR), clinical pregnancy rate (CPR) and miscarriage rate (MR) in fresh IVF or IVF-ICSI cycles. METHODS: This was a retrospective cohort study (n=170) involving patients attending the Centre for Reproductive and Genetic Health (CRGH) in London. The study cohort consisted of women undergoing controlled ovarian stimulation using GnRH antagonist or GnRH agonist protocols. Univariate and multiple logistic regression analyses were used to evaluate the association of clinical outcomes. Differences were considered statistically significant if p≤0.05. RESULTS: As serum progesterone increased, a decrease in LBR was observed. Following multivariate logistical analyses, LBR significantly decreased with P4 thresholds of 4.0 ng/ml (OR 0.42, 95% CI:0.17-1.0) and 4.5 ng/ml (OR 0.35, 95% CI:0.12-0.96). CONCLUSION: P4 levels are important in specific groups and the findings were statistically significant with a P4 threshold value between 4.0-4.5 ng/ml. Therefore, it seems logical to selectively measure serum P4 levels for patients who have ovarian dysfunction or an ovulatory cycles and accordingly prepare the individualized management packages for such patients.

Live birth and miscarriage rate following intracytoplasmic morphologically selected sperm injection vs intracytoplasmic sperm injection: An updated systematic review and meta-analysis.

INTRODUCTION: Intracytoplasmic morphologically selected sperm injection (IMSI) is one of the sperm selection techniques used for assisted reproduction which has been applied for a variety of indications including previously failed fertilization with intracytoplasmic sperm injection (ICSI). A Cochrane review1 found no difference in outcomes between either modality of sperm selection. Since the Cochrane review was published there have been a further two randomized controlled trials comparing IMSI and ICSI. This systematic review and meta-analysis aims to compare IMSI with ICSI as insemination methods regarding live birth rate and miscarriage rate. MATERIAL AND METHODS: Systematic review of randomized controlled trials, observational studies and similar reviews in electronic databases published before January 2018. RESULTS: We found nine randomized controlled trials, evaluating 1610 cycles of in vitro fertilization and 15 observational studies evaluating 1243 cycles of in vitro fertilization. Meta-analysis of the included randomized controlled trials showed no difference in the live birth rate or miscarriage rate between the ICSI and IMSI groups. Meta-analysis of five observational studies showed a significantly higher number of live births in the IMSI group than ICSI group (live birth rate odds ratio 1.47, 95% confidence interval 1.16-4.07), with a moderate degree of heterogeneity (I2  = 41%). Additionally, from six observational studies, a significantly lower miscarriage rate was observed in the IMSI group than in the ICSI group (odds ratio 0.51, 95% confidence interval 0.37-0.70, I2  = 0%). CONCLUSIONS: Meta-analysis of randomized studies comparing IMSI to ICSI has not shown any difference in live birth rate and miscarriage rate. Meta-analysis of observational studies, which must be interpreted with caution, revealed an increased live birth rate and decreased miscarriage rate with IMSI vs ICSI.

Assessment of ovarian reserve and reproductive outcomes in BRCA1 or BRCA2 mutation carriers.

INTRODUCTION: The clinical impact on fertility in carriers of BRCA1 and BRCA2 mutations remains unclear. The aim of this study was to assess ovarian reserve as measured by anti-mullerian hormone levels in BRCA1 or BRCA2 mutation carriers, as well as to investigate the impact of anti-mullerian hormone levels on reproductive outcomes. METHODS: The study involved a cohort of women who tested positive for BRCA1 and BRCA2 screening or were tested for a BRCA1 or BRCA2 family mutation. Blood samples were collected for anti-mullerian hormone analysis and the reproductive outcomes were analyzed after a mean follow-up of 9 years. Participants were classified into BRCA mutation-positive versus BRCA mutation-negative. Controls were healthy relatives who tested negative for the family mutation. All patients were contacted by telephone to collect data on reproductive outcomes. Linear regression was used to predict anti-mullerian hormone levels by BRCA status adjusted for a polynomial form of age. RESULTS: Results of anti-mullerian hormone analysis and reproductive outcomes were available for 135 women (BRCA mutation-negative, n=66; BRCA1 mutation-positive, n=32; BRCA2 mutation-positive, n=37). Anti-mullerian hormone curves according to BRCA status and adjusted by age showed that BRCA2 mutation-positive patients have lower levels of anti-mullerian hormone as compared with BRCA-negative and BRCA1 mutation-positive. Among the women who tried to conceive, infertility was observed in 18.7% of BRCA mutation-negative women, in 22.2% of BRCA1 mutation-positive women, and in 30.8% of BRCA2 mutation-positive women (p=0.499). In the multivariable analysis, there were no factors independently associated with infertility. DISCUSSION: BRCA2 mutation-positive carriers showed more diminished anti-mullerian hormone levels than BRCA1 mutation-positive and BRCA mutation-negative women. However, these differences do not appear to have a negative impact on reproductive outcome. This is important to consider at the time of reproductive counseling in women with BRCA1 or BRCA2 mutations.

The role of immunotherapy in in vitro fertilization and recurrent pregnancy loss: a systematic review and meta-analysis.

OBJECTIVE: To study the current evidence on the role of immunotherapy in IVF and in the management of recurrent pregnancy loss (RPL). DESIGN: Systematic review and meta-analysis. SETTING: A literature search was performed using MEDLINE, PUBMED, CINAHL, and EMBASE until May 2017. Only randomized controlled trials were included, and a meta-analysis was carried out where appropriate. PATIENT(S): Women undergoing IVF treatment with or without a history of recurrent implantation failure and women with idiopathic RPL. INTERVENTION(S): Assessment of the efficacy of commonly used immunomodulators such as IV use of [1] immunoglobulin, [2] lymphocyte immunotherapy and [3] intralipid; intrauterine infusion of [4] granulocyte colony-stimulating factor and [5] peripheral blood mononuclear cells; subcutaneous administration of [6] TNF-alpha inhibitors, [7] leukaemia inhibitory factor; and oral administration of [8] glucocorticoids. MAIN OUTCOME MEASURE(S): The primary outcomes were live birth rate and miscarriage rate; secondary outcome was clinical pregnancy rate. RESULT(S): Of the 7,226 publications identified, 53 were selected during the initial screening; 30 satisfied the selection criteria and were included in this review. CONCLUSION(S): The available medical literature shows controversial results about the role of immunotherapy when used for improving reproductive outcomes. This study did not show a role for immunotherapy in improving the live birth rate in women undergoing IVF treatment or in the prevention of idiopathic RPL. Currently, immunotherapy should be used in the context of research and should not be used in routine clinical practice to improve reproductive outcomes.

Tridimensional sonographic anatomical changes on pelvic floor muscle according to the type of delivery.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to evaluate the association of avulsion and postnatal hiatal dimensions with delivery mode. These anatomical changes on pelvic floor muscle may be assessed by 3-4D ultrasonography. METHODS: This is a prospective observational study that included 164 women: 20 nulliparous, 20 primigravid, and 124 postpartum women (62 at 1 month, 62 at 9 months postpartum). We performed an introital 3-4D ultrasonography to assess levator ani muscle's integrity, levator hiatal area at rest, on Valsalva, and on contraction. RESULTS: Levator ani avulsion was diagnosed in 59.5% of forceps deliveries. There were no statistically significant differences in postnatal hiatal dimensions between normal vaginal deliveries at 9 months postpartum and nulligravid. Levator hiatal area was significantly higher after forceps delivery. CONCLUSION: Low incidence of levator avulsion takes place in normal vaginal deliveries. However, forceps delivery is the riskiest type of delivery for pelvic floor pathology and its recovery.