Decidual Cell Polyploidization Necessitates Mitochondrial Activity

Cellular polyploidy has been widely reported in nature, yet its developmental mechanism and function remain poorly understood. In the present study, to better define the aspects of decidual cell polyploidy, we isolated pure polyploid and non-polyploid decidual cell populations from the in vivo decidual bed. Three independent RNA pools prepared for each population were then subjected to the Affymetrix gene chip analysis for the whole mouse genome transcripts. Our data revealed up-regulation of 1015 genes and down-regulation of 1207 genes in the polyploid populations, as compared to the non-polyploid group. Comparative RT-PCR and in situ hybridization results indeed confirmed differential expressional regulation of several genes between the two populations. Based on functional enrichment analyses, up-regulated polyploidy genes appeared to implicate several functions, which primarily include cell/nuclear division, ATP binding, metabolic process, and mitochondrial activity, whereas that of down-regulated genes primarily included apoptosis and immune processes. Further analyses of genes that are related to mitochondria and bi-nucleation showed differential and regional expression within the decidual bed, consistent with the pattern of polyploidy. Consistently, studies revealed a marked induction of mitochondrial mass and ATP production in polyploid cells. The inhibition of mitochondrial activity by various pharmacological inhibitors, as well as by gene-specific targeting using siRNA-mediated technology showed a dramatic attenuation of polyploidy and bi-nucleation development during in vitro stromal cell decidualization, suggesting mitochondria play a major role in positive regulation of decidual cell polyploidization. Collectively, analyses of unique polyploidy markers and molecular signaling networks may be useful to further characterize functional aspects of decidual cell polyploidy at the site of implantation

Installing oncofertility programs for common cancers in optimum resource settings (Repro-Can-OPEN Study Part II): a committee opinion

The main objective of Repro-Can-OPEN Study Part 2 is to learn more about oncofertility practices in optimum resource settings to provide a roadmap to establish oncofertility best practice models. As an extrapolation for oncofertility best practice models in optimum resource settings, we surveyed 25 leading and well-resourced oncofertility centers and institutions from the USA, Europe, Australia, and Japan. The survey included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed three major characteristics of oncofertility practice in optimum resource settings: (1) strong utilization of sperm freezing, egg freezing, embryo freezing, ovarian tissue freezing, gonadal shielding, and fractionation of chemo- and radiotherapy; (2) promising utilization of GnRH analogs, oophoropexy, testicular tissue freezing, and oocyte in vitro maturation (IVM); and (3) rare utilization of neoadjuvant cytoprotective pharmacotherapy, artificial ovary, in vitro spermatogenesis, and stem cell reproductive technology as they are still in preclinical or early clinical research settings. Proper technical and ethical concerns should be considered when offering advanced and experimental oncofertility options to patients. Our Repro-Can-OPEN Study Part 2 proposed installing specific oncofertility programs for common cancers in optimum resource settings as an extrapolation for best practice models. This will provide efficient oncofertility edification and modeling to oncofertility teams and related healthcare providers around the globe and help them offer the best care possible to their patients

Is there a Role for Conservative Treatment in Those With Unilateral Tubal Occlusion?

HSG is the accepted standard to diagnose tubal patency. In contrast to bilateral tubal occlusion where therapy is directed towards laparoscopic correction or IVF, treatment of unilateral tubal occlusion (UTO) is less clear, including conservative OI and IUI directed towards the patent tube. We assessed the value of conservative OI-IUI and pregnancy outcomes in those with UTO. Methods: We evaluated patients diagnosed on HSG with UTO (n=24) (proximal [n=7] and mid-distal or distal occlusion [n=17]). Inclusion included women \u3c38 years; regular menstrual cycles; normal sperm parameters; and normal spill from 1 fallopian tube on HSG. Controls underwent donor insemination (n=87 in 275 cycles) with bilateral tubal spill. Treatment included LH testing and time intercourse (n=5) or OI-IUI with Clomiphene Citrate or Letrazole (n=19 in 36 cycles). All treatment cycles were monitored by ultrasound; hCG was given when lead follicle size reached \u3e18mm (unless recruited follicle on obstructed side); and IUI was performed 24-36 hours later. The primary outcome measured was clinical pregnancy (CP). Results: Baseline demographics including age (32.2±4[±SD] vs 33.4±2 yrs, p-NS) and BMI (27.9±7 vs 28.2±8 kg/m2, p-NS) were similar between UTO and control groups. Between HSG and treatment, spontaneous pregnancy occurred in 5 (21%) women with UTO (1 proximal, 4 distal). In those undergoing OI-IUI treatment, CP rates/patient (32%, n=6/19 and 24%, n=21/87, p=0.56) and CP/cycle (17%, 6/36 and 8%, 21/275, p=0.10) were similar for UTO and control groups. Overall, CP occurred in 2 (29%) and 9 (53%) patients with proximal and mid-distal or distal UTO, p=0.005, respectively. Twenty-nine (81%) cycles recruited a dominant follicle on the patent side (19% CP/cycle), in contrast no pregnancies occurred (0%, 0/7) if recruitment occurred on the side of UTO, p=0.3. Conclusions: Pregnancy rates are not compromised in women with UTO and conservative treatment with OI-IUI appears justified as a first line approach, obviating more aggressive therapies including laparoscopy and IVF

Is there a Role for Conservative Treatment in Those With Unilateral Tubal Occlusion?

HSG is the accepted standard to diagnose tubal patency. In contrast to bilateral tubal occlusion where therapy is directed towards laparoscopic correction or IVF, treatment of unilateral tubal occlusion (UTO) is less clear, including conservative OI and IUI directed towards the patent tube. We assessed the value of conservative OI-IUI and pregnancy outcomes in those with UTO. Methods: We evaluated patients diagnosed on HSG with UTO (n=24) (proximal [n=7] and mid-distal or distal occlusion [n=17]). Inclusion included women \u3c38 years; regular menstrual cycles; normal sperm parameters; and normal spill from 1 fallopian tube on HSG. Controls underwent donor insemination (n=87 in 275 cycles) with bilateral tubal spill. Treatment included LH testing and time intercourse (n=5) or OI-IUI with Clomiphene Citrate or Letrazole (n=19 in 36 cycles). All treatment cycles were monitored by ultrasound; hCG was given when lead follicle size reached \u3e18mm (unless recruited follicle on obstructed side); and IUI was performed 24-36 hours later. The primary outcome measured was clinical pregnancy (CP). Results: Baseline demographics including age (32.2±4[±SD] vs 33.4±2 yrs, p-NS) and BMI (27.9±7 vs 28.2±8 kg/m2, p-NS) were similar between UTO and control groups. Between HSG and treatment, spontaneous pregnancy occurred in 5 (21%) women with UTO (1 proximal, 4 distal). In those undergoing OI-IUI treatment, CP rates/patient (32%, n=6/19 and 24%, n=21/87, p=0.56) and CP/cycle (17%, 6/36 and 8%, 21/275, p=0.10) were similar for UTO and control groups. Overall, CP occurred in 2 (29%) and 9 (53%) patients with proximal and mid-distal or distal UTO, p=0.005, respectively. Twenty-nine (81%) cycles recruited a dominant follicle on the patent side (19% CP/cycle), in contrast no pregnancies occurred (0%, 0/7) if recruitment occurred on the side of UTO, p=0.3. Conclusions: Pregnancy rates are not compromised in women with UTO and conservative treatment with OI-IUI appears justified as a first line approach, obviating more aggressive therapies including laparoscopy and IVF

A Pilot Randomized Trial of Levator Injections Versus Physical Therapy for Treatment of Pelvic Floor Myalgia and Sexual Pain

Introduction and hypothesis Our aim was to determine the effects of pelvic floor physical therapy (PT) and levator-directed trigger-point injections (LTPI) on sexual function and levator-related pelvic pain. Study design A randomized trial among women with pelvic floor myalgia (PFM) was performed wherein participants received either PT or LTPI. Pain was assessed and 1 month posttreatment completion. Levator-based pain was assessed using a numeric rating scale (NRS) and the Patient Global Impression of Improvement (PGI-I) scale. Sexual function was assessed using the Female Sexual Function Index (FSFI). Results Twenty-nine women completed the study (17 had PT, 12 had LTPI). Both groups reported reduction in vaginal pain: mean NRS change from baseline of 4.47 [standard deviation (SD) 2.12) for PT and 4.67 (SD 1.72) for LTPI (p = 0.8)]. A \u3e50 % improvement in NRS was documented among 59 % of women receiving PT and 58 % receiving LTPI (p = 1.0). Consistent with NRS scores, mean PGI-I score was 2.50 (SD 1.17) for PT and 2.17 (SD 1.01) for LTPI (p = 0.5). Mean change in FSFI favored PT [PT +8.87 (SD 5.60), LTPI +4.00 (SD 5.24), p = 0.04], reflecting improvement in the sexual pain domain favoring PT (p = 0.02). However, the time in weeks to effect improvement favored LTPI if controlling for the degree of change in NRS (p = 0.01) and FSFI (p = 0.01). Conclusions Vaginal myalgia and sex-related pain improved with pelvic floor PT and LTPI. Time-to-effect improvement and significance of therapy are dependent on treatment type

A Pilot Randomized Trial of Levator Injections Versus Physical Therapy for Treatment of Pelvic Floor Myalgia and Sexual Pain

Introduction and hypothesis Our aim was to determine the effects of pelvic floor physical therapy (PT) and levator-directed trigger-point injections (LTPI) on sexual function and levator-related pelvic pain. Study design A randomized trial among women with pelvic floor myalgia (PFM) was performed wherein participants received either PT or LTPI. Pain was assessed and 1 month posttreatment completion. Levator-based pain was assessed using a numeric rating scale (NRS) and the Patient Global Impression of Improvement (PGI-I) scale. Sexual function was assessed using the Female Sexual Function Index (FSFI). Results Twenty-nine women completed the study (17 had PT, 12 had LTPI). Both groups reported reduction in vaginal pain: mean NRS change from baseline of 4.47 [standard deviation (SD) 2.12) for PT and 4.67 (SD 1.72) for LTPI (p = 0.8)]. A \u3e50 % improvement in NRS was documented among 59 % of women receiving PT and 58 % receiving LTPI (p = 1.0). Consistent with NRS scores, mean PGI-I score was 2.50 (SD 1.17) for PT and 2.17 (SD 1.01) for LTPI (p = 0.5). Mean change in FSFI favored PT [PT +8.87 (SD 5.60), LTPI +4.00 (SD 5.24), p = 0.04], reflecting improvement in the sexual pain domain favoring PT (p = 0.02). However, the time in weeks to effect improvement favored LTPI if controlling for the degree of change in NRS (p = 0.01) and FSFI (p = 0.01). Conclusions Vaginal myalgia and sex-related pain improved with pelvic floor PT and LTPI. Time-to-effect improvement and significance of therapy are dependent on treatment type

Detection of the Dietary xenoglycan N-glycolylneuraminic Acid (Neu5Gc) and anti-Neu5Gc Antibodies within Reproductive Tracts of Male and Female Infertility Subjects

Objective To assess the frequency of dietary xenoglycanNeu5Gc and antibodies in males and females and its impact on fertility. Design Prospective study of semen, uterine lavage, and follicular fluid from subjects undergoing infertility evaluation or in vitro fertilization (IVF) and fertile controls. Setting University based infertility program. Participants Males (n=23) and females (n=27) undergoing semen analysis and saline infusion sonography as part of their diagnostic evaluation and 37 women undergoing IVF were compared to fertile male (n=15) and female (n=14) controls. Intervention Neu5Gc was measured by affinity purified antibody staining on Western blots, flow cytometry, and by high performance liquid chromatography. Anti-Neu5Gc antibodies were determined by ELISA. Main parameters measured Frequency and levels of Neu5Gc antigen within sperm and endometrial cells and antibodies in semen, uterine lavage, and follicular fluid. Semen quality and IVF outcomes were assessed between antigen and antibody positive and negative subjects. Results In infertile subjects, Neu5Gc was detected in 26% of sperm and 54% of endometrial cells compared to 0% in male and 0% female controls. Anti-Neu5Gc antibodies were identified in 54% of seminal fluid, 41% in uterine lavage and 43% of follicular fluid samples. There were no differences in semen parameters, oocyte quality, and embryo development in the presence or absence of Neu5Gc antigen or antibody. However, clinical pregnancy rate was significantly lower in the presence of anti-Neu5Gc antibodies intrauterine lavage (0% vs. 54.5.0%, p\u3c0.05). Conclusions Neu5Gc and directed antibodies are present in reproductive tracts of both male and female infertility subjects. Our results suggest their presence may interfere with fertility within the uterine environment

Hysterosalpingo‐Contrast Sonography With a Saline‐Air Device Is Equivalent to Hysterosalpingography Only in the Presence of Tubal Patency

Objectives To compare hysterosalpingo‐contrast sonography with a saline‐air device to hysterosalpingography for evaluating tubal patency. Methods Eighty women undergoing infertility evaluations were recruited for this prospective cohort study. All patients underwent both office‐based hysterosalpingo‐contrast sonography with a saline‐air device and hysterosalpingography as the reference standard, and the fallopian tubes were individually assessed for tubal patency in each procedure. The Cohen κ coefficient was used to assess agreement between each procedure, and the Student t test and χ2 test were used to compare differences in time, pain, and procedural preference. Results In total, 75 patients with 148 fallopian tubes were evaluated. Tubal patency on hysterosalpingo‐contrast sonography with the saline‐air device was noted in 85.8% (n = 127) of tubes compared to 92.5% (n = 137) on hysterosalpingography, with a positive predictive value of 95.2%. Tubal occlusion was noted in 21 tubes (14.2%) on hysterosalpingo‐contrast sonography compared to 11 (7.4%) on hysterosalpingography, with a negative predictive value of 23.8% (24 of 28). Overall, hysterosalpingo‐contrast sonography agreed with hysterosalpingography in 126 of 148 fallopian tubes (85.1%; κ = 0.47; P \u3c .001). The procedural time and pain scores were significantly greater for hysterosalpingo‐contrast sonography compared to hysterosalpingography. Conclusions There was a significant degree of agreement between hysterosalpingo‐contrast sonography with a saline‐air device and hysterosalpingography when the fallopian tube was patent but not when it was occluded. In the absence of patency, further evaluations with hysterosalpingography may be indicated to avoid false‐positive results. Although the procedure time and degree of pain appear to be greater, avoidance of radiation exposure by using hysterosalpingo‐contrast sonography with a saline‐air device may outweigh the drawbacks