Elevated Adipsin and Reduced C5a Levels in the Maternal Serum and Follicular Fluid During Implantation Are Associated With Successful Pregnancy in Obese Women.

Introduction: Complement factors mediate the recruitment and activation of immune cells and are associated with metabolic changes during pregnancy. The aim of this study was to determine whether complement factors in the maternal serum and follicular fluid (FF) are associated with in vitro fertilization (IVF) outcomes in overweight/obese women. Methods: Forty overweight/obese (BMI = 30.8 ± 5.2 kg/m2) female patients, 33.6 ± 6.3 years old, undergoing IVF treatment for unexplained infertility were recruited. Baseline demographic information, including biochemical hormonal, metabolic, and inflammatory markers, and pregnancy outcome, was collected. Levels of 14 complement markers (C2, C4b, C5, C5a, C9, adipsin, mannose-binding lectin, C1q, C3, C3b/iC3b, C4, factor B, factor H, and properdin) were assessed in the serum and FF and compared to IVF outcome, inflammatory, and metabolic markers using multivariate and univariate models. Results: Out of 40 IVF cycles, 14 (35%) resulted in pregnancy. Compared to women with failed pregnancies, women with successful pregnancies had higher levels of adipsin in the serum and FF (p = 0.01) but lower C5a levels (p = 0.05). Serum adipsin levels were positively correlated with circulating levels of vitamin D (R = 0.5, p = 0.02), glucagon (R = 0.4, p = 0.03), leptin (R = 0.4, p = 0.01), resistin (R = 0.4, p = 0.02), and visfatin (R = 0.4, p = 0.02), but negatively correlated with total protein (R = -0.5, p = 0.03). Higher numbers of top-quality embryos were associated with increased levels of C3, properdin, C1q, factors H and B, C4, and adipsin, but with reduced C2 and C5a levels (p ≤ 0.01). Conclusions: Higher adipsin and lower C5a levels in the maternal serum during implantation are potential markers of successful outcome in obese women undergoing IVF-assisted pregnancies.

The effect of paternal age on intracytoplasmic sperm injection outcome in unexplained infertility.

OBJECTIVE: : To examine the effect of paternal age on intracytoplasmic sperm injection (ICSI) outcomes in unexplained infertility. SUBJECTS AND METHODS: : This retrospective study, done at the Hamad Medical Corporation, Doha, Qatar screened infertile couples who underwent ICSI between 2014 and 2019 for the inclusion and exclusion criteria defining 'unexplained infertility'. Couples recruited were allocated into two groups: Group A (paternal age <35 years) and Group B (paternal age ≥35 years). Baseline characteristics, investigations including semen and advanced sperm function tests and ICSI records were compared for primary outcomes such as fertilisation, cleavage, clinical pregnancy, miscarriage and live birth; and secondary outcomes such as semen parameters and advanced sperm functions (DNA fragmentation index and oxidation reduction potential). RESULTS: : We found that final pregnancy outcomes including clinical pregnancy rate (P = 0.231), live-birth rate (P = 0.143), and miscarriage rates (P = 0.466) were not significantly different between the two age groups. Normal fertilisation (P = 0.01) and cleavage rate after ICSI (P = 0.001) were statistically significant when the age groups were compared. Also, normal sperm morphology was found to be significantly different (P = 0.041). CONCLUSIONS: : Advanced paternal age affects sperm morphology, fertilisation and embryo cleavage in ICSI but does not appear to affect clinical pregnancy, miscarriage or live-birth rates. ICSI appears to be a valid fertility treatment option in advancing paternal age.

The effect of sperm DNA fragmentation on intracytoplasmic sperm injection outcome.

Our study objective was to assess the effect of various sperm DNA fragmentation levels on clinical intracytoplasmic sperm injection outcome. This retrospective study included 392 patients who underwent ICSI and performed sperm DNA fragmentation testing before the procedure. Based on sperm DNA fragmentation cut-off values, the patients were differentiated into 3 groups as <20%, 20%-30% and >30%. According to the female status, patients were differentiated into favourable group (n = 259) with female age <35 years and anti-Mullerian hormone level ≥7.1 pmol/L; and unfavourable group (n = 133) with female age ≥35 years and anti-Mullerian hormone level ≤7.1 pmol/L. The patient's medical records were reviewed, and patient's demographic, laboratory data including semen analysis, sperm DNA fragmentation determined by means of sperm chromatin dispersion, hormonal profile and data regarding intracytoplasmic sperm injection cycle were collected. This cohort reported that the clinical reproductive outcomes of intracytoplasmic sperm injection showed no statistical significance with increase sperm DNA fragmentation levels. In sperm DNA fragmentation above 30%, favourable females had significantly higher clinical pregnancy rate and live birth rate than unfavourable females, while fertilisation rate and miscarriage rate showed no significance between the subgroups. High sperm DNA fragmentation is linked to poor semen parameters.

Predictive model to estimate the chances of successful sperm retrieval by testicular sperm aspiration in patients with nonobstructive azoospermia.

OBJECTIVE: To explore predictors of successful sperm retrieval (SR) and to identify potentially suitable candidates for testicular sperm aspiration (TESA), a more straightforward, less traumatic, and less costly procedure than open surgical SR methods. DESIGN: Retrospective chart review. SETTING: Academic tertiary medical center. PATIENTS: A total of 297 patients with nonobstructive azoospermia. INTERVENTIONS: All patients underwent full clinical evaluation before undergoing a staged SR procedure, starting with TESA and proceeding to microsurgical testicular sperm extraction (microTESE). Predictors of positive SR with TESA were selected using the least absolute shrinkage and selection operator (LASSO) regression analysis using k-fold cross-validation. The obtained regression coefficients were used to create a predictive model, and a receiver operating characteristic (ROC) curve was obtained to express its predictive ability. Cut-off values for each significant predictor were also identified using ROC analysis. MAIN OUTCOME MEASURE(S): Development of a prediction model for positive SR with TESA. RESULTS: Overall, a positive SR was observed in 23.6% of patients undergoing TESA. Average testis size (P = .017) and serum follicle-stimulating hormone (FSH) level (P < .001) were the significant predictors of positive SR identified by LASSO regression analysis. The predictive model had an AUC of 0.742 with a sensitivity of 73.9% and specificity of 69.9%. Patients presenting with an average testis size >7.75 mL and serum FSH level <8.5 IU/L had a TESA-positive SR of 43%. CONCLUSIONS: TESA may be a suitable alternative to microTESE in selected nonobstructive azoospermia patients presenting with an average testis size >7.75 mL and serum FSH level <8.5 IU/L.

Seminal hyperviscosity is not associated with semenogelin degradation or sperm deoxyribonucleic acid damage: a prospective study of infertile couples.

OBJECTIVE: To investigate the association between seminal hyperviscosity, the extent of semenogelin degradation, and sperm DNA integrity (DNA fragmentation index [DFI] and high DNA stainability [HDS]) in semen from infertile couples. DESIGN: Prospective study. SETTING: University-affiliated fertility center. PATIENT(S): Twenty-four consecutive infertile couples with moderate or high seminal viscosity (hyperviscosity group) and 25 consecutive infertile couples with normal semen viscosity (control group) undergoing standard IVF. INTERVENTION(S): Semen volume and seminal hyperviscosity, sperm concentration, motility, and morphology, level of semenogelin degradation (by immunoblotting), and sperm chromatin damage (by sperm chromatin structure assay and expressed as %DFI and %HDS) were evaluated. MAIN OUTCOME MEASURES(S): Sperm %DFI and %HDS in the hyperviscosity group and the control group and the relationship between the extent of semenogelin degradation and seminal viscosity. RESULT(S): Semen volume in couples with moderate and high seminal viscosity was significantly lower as compared with the control group. In addition, total motility and normal morphology were significantly lower in the couples with high seminal viscosity as compared with the control group; however, there were no significant differences in sperm %DFI and %HDS between the hyperviscosity group and the control group. In addition, there was no relationship between the extent of semenogelin degradation and seminal viscosity. CONCLUSION(S): Our data suggest that seminal hyperviscosity (a posttesticular factor) is not an important cause of sperm DNA damage. Moreover, seminal hyperviscosity is not related to the degree of semenogelin degradation.

Monozygotic twins in infertile patients with advanced maternal age: case reports and review of the literature.

OBJECTIVE: To report two cases of successful monozygotic twin pregnancies in women undergoing infertility treatment and to review possible etiologic factors. DESIGN: Case report and review of the literature. SETTING: University of Toronto-affiliated infertility clinic. PATIENT(S): A 43-year-old woman and a 44-year-old woman with history of secondary infertility. INTERVENTION(S): In vitro fertilization and ET. MAIN OUTCOME MEASURE(S): Monozygotic twin pregnancy. RESULT(S): Delivery of two sets of monozygotic twins. CONCLUSION(S): The only identified potential risk factors for monozygotic twins are maternal age and assisted reproductive technologies. Both patients reported here were aged >40 years and underwent assisted reproduction procedures, including high-dose gonadotropin stimulation, embryo culture, and, in case 2, intracytoplasmic sperm injection plus assisted hatching.

Ongoing twin pregnancy after rescue intracytoplasmic sperm injection of unfertilized abnormal oocytes.

OBJECTIVE: To report a case of an ongoing twin pregnancy resulting from rescue intracytoplasmic sperm injection (ICSI) after failed fertilization of morphologically abnormal oocytes. DESIGN: Case report. SETTING: Tertiary center for assisted reproductive technology (ART). PATIENT(S): A 28-year-old woman with primary infertility due to tubal obstruction. INTERVENTION(S): Rescue ICSI after failed IVF insemination. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Successful ongoing twin pregnancy. CONCLUSION(S): With failed fertilization of oocytes with abnormal morphology after IVF, early rescue ICSI may increase the fertilization rates and result in an ongoing pregnancy.

Seminal hyperviscosity is associated with poor outcome of in vitro fertilization and embryo transfer: a prospective study.

OBJECTIVE: To investigate the effect of increased seminal viscosity on fertilization, implantation, and pregnancy outcome in patients undergoing in vitro fertilization/ intracytoplasmic sperm injection (ICSI). DESIGN: Prospective study. SETTING: University-affiliated infertility center. PATIENT(S): One hundred fifty-eight infertile couples (168 cycles) with increased seminal viscosity and 129 infertile couples (138 cycles) with normal seminal viscosity as controls. INTERVENTION(S): In vitro fertilization using conventional insemination or ICSI. MAIN OUTCOME MEASURE(S): Fertilization, embryo quality, implantation, and pregnancy rates (PR) were evaluated. RESULT(S): Patient age and the cause of infertility were similar between the two groups. Sperm count (36.9 +/- 34.0 vs. 28.1 +/- 25.6) and motility (41.5 +/- 19.2 vs. 37.0 +/- 20.5) was higher in the control group compared to the study group. Fertilization rate after IVF (50.4% vs. 64.6%), clinical PR (28% vs. 39.9%), and the implantation rates (10.5% vs. 16.5%) were significantly lower in patients with hyperviscosity compared to the control group. CONCLUSION(S): The lower implantation rate and clinical PR in couples with seminal hyperviscosity may be attributed to biophysical alterations or chemical changes of the ejaculate that could impact sperm DNA despite the presence of apparently normal motile sperm for the IVF/ICSI procedure.

Brown oocytes: implications for assisted reproductive technology.

Fertilization, embryo development, and successful pregnancy can be achieved after transfer of embryos derived from brown oocytes at the same rate as embryos from morphologically normal oocytes. Therefore, brown oocytes are probably normal and this morphological criterion does not seem to be indicative of any adverse outcome in IVF.