Direct conversion from long-acting testosterone replacement therapy to Natesto allows for spermatogenesis resumption: Proof of concept.

Long-acting testosterone replacement therapy (TRT) suppresses spermatogenesis. A short-acting TRT, Natesto, maintains spermatogenesis in some men. This study evaluated hormonal and semen parameters converting men from long-acting TRT to Natesto. Baseline hormones, again on long-acting TRT and 1 month after converting to Natesto, as well as semen parameters 3 months after converting to Natesto were assessed. Twenty-seven men were directly converted from long-acting forms of TRT to Natesto. Mean duration on long-acting TRT was 24.3 ± 19 months. Testosterone levels were similar on long-acting forms of TRT and Natesto, however; E2 levels were significantly lower on Natesto. Ten men had semen analyses demonstrating azoospermia while on long-acting TRT, the remainder were presumed to be azoospermic or severely oligospermic which has been well established as an effect of long-acting TRT. All 27 men had resumption of spermatogenesis with a mean sperm concentration of 50.7 million/ml after converting to Natesto, considered within the fertile range. One couple achieved a pregnancy 4 months after converting to Natesto. Hypogonadal men on long-acting TRT interested in resumption of spermatogenesis may convert directly to Natesto for an opportunity to do so while remaining on a form of TRT and achieving lower E2 levels.

Varicocele Repair Improves Static Oxidation Reduction Potential as a Measure of Seminal Oxidative Stress Levels in Infertile Men: A Prospective Clinical Trial Using the MiOXSYS System.

OBJECTIVE: To assess whether varicocele repair improves oxidative stress (OS) measured by the MiOXSYS system. METHODS: A prospective clinical trial was performed on male patients ages 18 and older who had not fathered a child within the previous 12 months, with a clinically palpable varicocele, who completed all aspects of the study who were enrolled through a couple's fertility center with on-site andrology laboratory testing. Men that met inclusion criteria were offered enrollment in the clinical trial and signed informed consents to participate, after having a history and physical examination. Semen analysis with OS measurement was obtained preoperatively and repeat semen analysis with OS measurement obtained 3 months following varicocele repair. Changes in postoperative semen analysis parameters, static oxidation reduction potential (sORP), and sperm DNA fragmentation (SDF) indices when available were compared to these values preoperatively. RESULTS: Of the 177 subjects, 49 subjects met inclusion criteria. The data of OS suggests negative correlations with major semen parameters. Semen parameters and OS revealed statistically significant improvements following varicocele repair from baseline. Of the 49 subjects included, 22 completed all aspects of testing postoperatively. Subgroup analysis shows statistically significant negative correlations between OS and semen parameters. Forward progressive motility, SDF, and sORP demonstrated statistically significant improvements 3 months following varicocele repair in comparison to preoperatively. CONCLUSION: Varicocele repair in infertile men improved sORP as measured by the clinically useful MiOXSYS system.

The expression of pregnancy-associated plasma protein-A (PAPP-A) in human blastocoel fluid-conditioned media: a proof of concept study.

PURPOSE: The aim of this study was to determine if pregnancy-associated plasma protein-A (PAPP-A), typically measured in maternal serum and a potential predictor of adverse maternal and fetal outcomes such as spontaneous miscarriage, pre-eclampsia, and stillbirth, is expressed in blastocoel fluid-conditioned media (BFCM) at the embryonic blastocyst stage. DESIGN: This is an in vitro study. METHODS: BFCM samples from trophectoderm-tested euploid blastocysts (n = 80) from in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients were analyzed for PAPP-A mRNA. BFCM was obtained from blastocyst stage embryos in 20 uL drops. Blastocysts underwent trophectoderm biopsy for preimplantation genetic testing for aneuploidy prior to blastocyst vitrification and BFCM collection for snap freezing. cfDNA was synthesized using BFCM collected from 80 individual euploid blastocysts. Next, real-time qPCR was performed to detect expression of PAPP-A with GAPDH for normalization of expression in each sample. RESULTS: PAPP-A mRNA was detected in 45 of 80 BFCM samples (56.3%), with varying levels of expression across samples. CONCLUSION: Our study demonstrates the expression of PAPP-A in BFCM. To our knowledge, this is the first study to report detection of PAPP-A mRNA in BFCM. Further studies are required and underway to investigate a greater number of BFCM samples as well as the possible correlation of PAPP-A expression with pregnancy outcomes of transferred euploid blastocysts. If found to predict IVF and obstetric outcomes, PAPP-A may provide additional information along with embryonic euploidy for the selection of the optimal blastocyst for embryo transfer.

The effects of hysteroscopic morcellation of endometrial polyps on frozen embryo transfer outcomes.

OBJECTIVE(S): To determine if hysteroscopic removal of endometrial polyps, specifically via morcellation of polyps, affects implantation rate (IR), clinical pregnancy rate (CPR), spontaneous abortion (SAB) rate, and live birth rate (LBR) in first frozen embryo transfer (FET) cycles. STUDY DESIGN: Retrospective chart review, with data abstracted from the charts of all first autologous oocyte frozen embryo transfer (FET) cases (n = 135) at a single fertility center from January 2018 through June 2020. Subjects were grouped into (A) hysteroscopic polypectomy prior to first FET (n = 25) or (B) no hysteroscopic polypectomy prior to first FET (n = 110). The primary outcome was live birth rate (LBR). Secondary outcomes were implantation rate (IR), clinical pregnancy rate (CPR), and spontaneous abortion (SAB) rate. RESULTS: We found no difference between the groups in terms of the primary outcome (LBR) or the secondary outcomes IR, CPR, and SAB rate. CONCLUSION(S): The data analyzed here suggest that hysteroscopic morcellation of endometrial polyps has no adverse effect on IR, SAB rate, CPR, or LBR among first FET cases after this type of polypectomy.

FSH levels and testicular volumes are associated with the severity of testicular histopathology in men with non-obstructive azoospermia.

PURPOSE: The purpose of this study is to assess a potential association between FSH levels and testicular volumes with the severity of testicular histopathology on testicular biopsy in men with non-obstructive azoospermia (NOA) undergoing microdissection testicular sperm extraction (microTESE). METHODS: A retrospective chart review was performed from the electronic health records of men who underwent microTESE with NOA. RESULTS: Eighty-six men with NOA underwent microTESE with concomitant testicular biopsy for permanent section to assess the testicular cellular architecture. The histopathological patterns were categorized by severity indicating the odds of sperm retrieval into 2 categories. The unfavorable category included Sertoli cell only pattern and early maturation arrest (n = 50) and the favorable category included late maturation arrest and hypospermatogenesis patterns (n = 36). In the men with unfavorable histopathologic patterns, the mean FSH level was 22.9 ± 16.6 IU/L, and the mean testicular volume was 10.4 ± 6.0 cc. This was in comparison to men with favorable histopathologic patterns revealing a mean FSH level of FSH 13.3 ± 12.0 with a mean testicular volume of 13.3 ± 5.9 cc. There was a statistically significant higher FSH level in men with unfavorable histopathology than favorable (p = 0.004) as well as a significant smaller mean testicular volume in men with unfavorable histopathology (p = 0.029). CONCLUSIONS: Higher serum FSH levels and smaller testicular volumes are associated with more severe testicular histopathological patterns in men with NOA.

The impact of ipsilateral testicular atrophy on semen quality and sperm DNA fragmentation response to varicocele repair.

Varicoceles adversely impact semen quality and sperm DNA fragmentation, which typically improve with surgical repair. Some men with varicoceles have ipsilateral testicular atrophy due to damage from the varicocele. This study assessed semen quality and the sperm DNA fragmentation index (DFI) response to varicocele repair in men with ipsilateral testicular atrophy (TA) versus men with no testicular atrophy (NTA). Semen parameter values and DFI in both groups were compared preoperatively and postoperatively. The Mann-Whitney U test and the Wilcoxon signed-rank test were used where appropriate. There were 20 men in the TA group and 121 men in the NTA group with no difference in age, varicocele grade, or preoperative semen parameter values between the two groups. The NTA group had a higher preoperative DFI than the TA group. Both groups showed improvement in semen quality postoperatively, only the TA group showed a significant improvement in DFI, whereas the NTA group showed significant improvements in several parameter values and DFI. The change from preoperative to postoperative parameter values when comparing the two groups revealed a difference in total sperm motile count and DFI, with a larger mean improvement in the NTA group than in the TA group. Both TA and NTA groups showed improved semen quality and DFI after varicocele repair, but the NTA group had more improvement than the TA group. However, only total motile count (TMC) and DFI had a significantly greater mean change in preoperative to postoperative response in the NTA group than in the TA group.

Converting Men From Clomiphene Citrate to Natesto for Hypogonadism Improves Libido, Maintains Semen Parameters, and Reduces Estradiol.

OBJECTIVE: To evaluate outcomes including libido, semen parameters, testosterone, estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone when converting men with low libido on Clomiphene Citrate (CC) to Natesto. METHODS: A retrospective chart review was performed. Baseline hormones prior to treatment, and again on CC and Natesto, as well as semen parameters on CC and on Natesto were assessed. RESULTS: In 41 men, there was no difference in serum testosterone levels on CC vs Natesto, however; there was a significantly higher E2 on CC than on Natesto. Although FSH levels were significantly lower on Natesto than at baseline, the mean FSH level on Natesto remained in the normal reference range. There was no difference in luteinizing hormone levels at baseline vs on Natesto. There was not a significant difference in semen parameter values when men were on CC vs when they were on Natesto for 3 months. At 3 months after changing to Natesto, 38 of 41 (92.7%) men reported significantly improved libido on Natesto when compared to CC. CONCLUSION: Men on CC and Natesto reach eugonadal testosterone levels, however; on CC the E2 level nearly doubled from baseline, and converting men from CC to Natesto returned E2 to nearly baseline levels. There was not a detrimental effect on semen parameters, and there was subjective reporting of improved libido after converting from CC to Natesto in this cohort, but further long-term studies are needed prior to Natesto being established as a definitive treatment for hypogonadism for men desiring to maintain fertility.

A comprehensive assessment of predictors of fertility outcomes in men with non-obstructive azoospermia undergoing microdissection testicular sperm extraction.

BACKGROUND: Microdissection testicular sperm extraction (microTESE) in men with non-obstructive azoospermia (NOA) is the procedure that results in the highest number of sperm cells retrieved for in vitro fertilization (IVF). This study presents a novel assessment of predictors of sperm retrieval as well as downstream embryology and pregnancy outcomes in cases of men with NOA undergoing microTESE. METHODS: A retrospective chart review of 72 men who underwent microTESE for predictors of fertility outcomes including sperm retrieved at microTESE, embryology progression to embryo transfer (ET), clinical pregnancy, live birth, and surplus sperm retrieved for additional IVF/intracytoplasmic injection cycles beyond one initial cycle. Statistical models for each of these outcomes were fitted, with a p-value of < 0.05 considered significant for the parameters estimated in each model. RESULTS: Seventy-two men underwent microTESE, and 51/72 (70.8%) had sperm retrieved. Of those, 29/43 (67.4%) reached ET. Of the couples who underwent ET, 21/29 (72.4%) achieved pregnancy and 18/29 (62.1%) resulted in live birth. Of the men with sperm retrieved, 38/51 (74.5%) had surplus sperm cryopreserved beyond the initial IVF cycle. Age, testicular volume, FSH, and testicular histopathology were assessed as predictors for sperm retrieved at microTESE, progression to ET, pregnancy, live birth, and surplus sperm. There were no preoperative predictors of sperm retrieval, clinical pregnancy, or live birth. Age predicted reaching ET, with older men having increased odds. FSH level had a negative relationship with surplus sperm retrieved. Men with hypospermatogenesis histology had higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm. CONCLUSIONS: Men who underwent microTESE with a hypospermatogenesis histopathology had better outcomes, including higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm retrieved. Increasing male partner age increased the odds of reaching ET. No other clinical factors were predictive for the outcomes considered.

Factors associated with subchorionic hematoma formation in pregnancies achieved via assisted reproductive technologies.

PURPOSE: To determine if certain clinical and/or embryologic factors are independently associated with the increased prevalence of subchorionic hematoma (SCH) among pregnancies achieved via in vitro fertilization (IVF) with fresh embryo transfer (ET). DESIGN: Retrospective chart review. METHODS: In this retrospective study, data were abstracted from 210 autologous oocyte IVF clinical pregnancies that resulted from fresh ET at a single fertility center from January 2012 through December 2016. Clinical and embryology laboratory variables were analyzed as possible factors associated with the presence or absence of SCH in IVF pregnancies via bivariate associations and multivariable logistic regression analyses. Independent variables included prior uterine surgery versus no uterine surgery, peak estradiol, and progesterone levels, day 3 (n = 92) versus day 5 (n = 118) ET, and assisted hatching versus no assisted hatching. Among the day 5 ET subgroup of 118 patients, 117 had data for the variables inner cell mass (ICM) grading and trophectoderm (TE) because one day 5 ET was at the morula stage. RESULTS: We found a significant bivariate association between TE grading and SCH, where cases with TE grade "A" were significantly less likely to have SCH compared with cases with grades "B" or "C." This significant difference remained when adjusting for the other factors considered in a multivariable logistic regression model for the probability of SCH. CONCLUSIONS: The data analyzed here suggest that a less-advanced trophectoderm grade may be a potential factor that is associated with the presence of SCH in pregnancies achieved via IVF.

Sertoli cell only syndrome induced by a varicocele.

A case is reported which describes the severity of testicular histological damage that can be induced by a high-grade varicocele in a male with secondary infertility. A chart review of a patient's case was performed. A 34-year-old male with a three-and-a-half-year-old son who was conceived spontaneously with timed intercourse, with a grade three left varicocele, who's semen parameters progressed to non-obstructive azoospermia (NOA). He did not regain sperm in the ejaculate three or six months post left subinguinal microsurgical varicocele repair. He underwent bilateral microdissection testicular sperm extraction (microTESE) without identification of sperm in the testicular samples. A testicular biopsy from the time of microTESE revealed a Sertoli cell only pattern. A high-grade varicocele has the potential to induce sufficient testicular damage to result in the most severe testicular histological architecture associated with non-obstructive azoospermia (NOA), Sertoli cell only syndrome (SCOS).

Serum Antimüllerian hormone does not predict elevated progesterone levels among women who undergo controlled ovarian hyperstimulation for in vitro fertilization.

Serum Antimüllerian hormone (AMH) has been shown to predict various in vitro fertilization (IVF) outcomes. AMH and progesterone (P) are products of granulosa cells of the ovary. Since overall granulosa cell number directly correlates with oocyte number and AMH production, the aim of this study is to evaluate whether or not serum AMH is associated with elevated P during controlled ovarian hyperstimulation (COH) for IVF. For this retrospective study, data were abstracted from charts of first IVF cycles of women (n = 201) who had undergone COH between May 2014 and May 2017. Groups were as follows: (A) AMH < 1 ng/mL (n = 32), (B) AMH 1-3.99 ng/mL (n = 109), (C), AMH ≥ 4 ng/mL (n = 60). The primary outcome measure was serum P level at trigger prior to oocyte retrieval. Mean serum P levels among groups A, B, and C were 0.92 ng/mL, 0.96 ng/mL, and 0.84 ng/mL, respectively. One-way ANOVA showed that there was no difference in mean serum P level among groups A, B, and C (p-value = 0.28). Multivariable linear regression with P as the dependent variable showed that total gonadotropin dose and peak estradiol level on day of trigger each had a significant positive relationship with P, and clinical pregnancy had a significant negative relationship. Although AMH is a predictor of certain IVF outcomes, AMH is not a predictor of elevated serum P level at trigger among women who undergo COH for IVF.

Medical Treatments for Hypogonadism do not Significantly Increase the Risk of Deep Vein Thrombosis Over General Population Risk.

OBJECTIVE: To evaluate the risk of deep vein thrombosis (DVT) in men treated with testosterone replacement therapy (TRT) or Clomiphene Citrate (CC) and assess other etiologies for DVT as contributing factors. METHODS: Retrospective chart review of 1180 consecutive hypogonadal men who were treated with either TRT or CC. Sixty-four percent had mixed, 16% had primary, and 20% had secondary hypogonadism. RESULTS: Of the 1180 men with hypogonadism, 694 were treated with TRT, while 486 were treated with CC. Overall, 10 of 1180 (0.8%) men were diagnosed with a DVT during the treatment, 9 of whom were on TRT and 1 on CC. Of the 10 men diagnosed with DVT while on treatment, 7 (70%) had potential identifiable etiologies for DVT other than treatment for hypogonadism. None of the men were found to be polycythemic at the time of DVT diagnosis. There was a higher incidence of DVT in men treated with TRT than CC, however; the overall percentages of DVT in both treatment groups were relatively low. There was no difference in the percentages of men found to have other identifiable etiologies for DVT besides being on treatment between the TRT and CC groups. There was not a difference in testosterone levels between the TRT and CC groups. CONCLUSION: The overall rates of DVT for TRT and CC treated patients are relatively low, and the majority of patients with DVT had other identifiable etiologies for DVT. Polycythemia was not found to be a risk factor in the patients diagnosed with DVTs.

Robot-assisted microsurgical vasovasostomy: the learning curve for a pure microsurgeon.

Vasovasostomy success rates improved with the application of the operative microscope in 1975. The robotic platform offers potential advantages including: a stable, ergonomic, scalable control system with three-dimensional visualization and magnification, the elimination of physiological tremor, and simultaneous control of three instruments and a camera. A previous publication revealed a fellowship-trained microsurgeon (PKK) could transition to robot-assisted microsurgical vasovasostomy (RAVV) with comparable outcomes. The objective of this current study was to evaluate the learning curve for the purely trained microsurgeon transitioning to RAVV. A retrospective chart review was performed of a microsurgeon's first 100 RAVVs evaluating the learning curve for patency rates, anastomosis times, operative times, and sperm concentrations at the initial postoperative semen analyses. Cases were stratified into four groups by 25 case intervals. There were no statistically significant differences in patency rates or postoperative sperm concentrations between the groups over time. There were differences in anastomosis times between groups 1 and 2, as well as between groups 2 and 3, and there were differences in operative times between groups 2 and 3. High-percentage patency rates are achievable very early in the transition from pure microsurgical vasovasostomy to RAVV across wide ranges of obstructive intervals. Postoperative mean sperm concentrations in the initial semen analyses after RAVV are consistent over time. For a single microsurgeon not formally trained in robotic microsurgery, 75 RAVV cases were required to optimize and plateau in anastomosis times and 75 cases were required to optimize operative times.

Ibuprofen does not have an adverse impact on semen parameters.

PURPOSE: A recent study suggested that ibuprofen may alter testicular physiology in a state of compensated hypogonadism, but only evaluated spermatogenic cells in a laboratory ex-vivo model with no significant effect, and found no significant change in follicle stimulating hormone (FSH) in men treated with ibuprofen. The study did not evaluate the impact of ibuprofen use on clinical semen parameters, which has not been assessed to date. The purpose of this study was to evaluate the impact of ibuprofen on semen parameters. METHODS: In a retrospective chart review from October 2012 to February 2018, 64 men had semen analyses revealing leukocytospermia and were treated with a 3-week course of ibuprofen 600 mg every 8 hours (1800 mg per day) and had a repeat semen analyses 3 weeks later. RESULTS: Of the 64 men diagnosed with leukocytospermia, 51 returned for post-treatment semen analyses. Parameters included semen volume, sperm concentration, motility, TMC, and forward progression. Morphology was excluded as it could not be standardized between assessments with strict Kruger criteria versus WHO fourth edition criteria depending on the lab in which it was performed. The mean age of these men was 35 (SD 4.6). There was no difference in mean abstinence intervals prior to semen analyses for the pre-treatment and post-treatment data. There was no significant difference in pre-treatment and post-treatment semen volumes, sperm concentrations, motility, TMC, or forward progression. CONCLUSIONS: Among men with leukocytospermia, the treatment with a 3-week course of ibuprofen at 1800 mg per day did not demonstrate a significant adverse impact on semen volume, sperm concentration, motility, TMC, or forward progressive motility when compared to pre-treatment semen analyses parameters.

Promescent Has a Cytotoxic Impact on Fresh Human Sperm In Vitro.

OBJECTIVE: To assess the impact of Promescent, a commonly used topical medication for premature ejaculation (PE), on human sperm motility, forward progression (FP), viability, and sperm DNA fragmentation (SDF) in vitro. MATERIALS AND METHODS: Aliquots from specimens for diagnostic semen analyses from patients (n = 20) presenting to a couple's fertility center andrology laboratory for fertility testing were included after the full diagnostic semen analyses were performed. Samples that met the World Health Organization's fifth edition criteria as "normal" had Promescent applied to an aliquot of the sample and motility, FP, viability, and SDF were compared with an aliquot that was not treated with Promescent. Institutional review board exemption was obtained. Statistical analysis was performed by Student t test with a P value of <.05 considered as statistically significant. RESULTS: Promescent had a cytotoxic effect on sperm, which resulted in a statistically significant decrease in mean motility, FP, and viability as compared with corresponding control group samples, which did not have Promescent applied. There was no statistically significant difference in SDF between the 2 groups. CONCLUSION: PE is estimated to affect up to 39% of men and is one of the most common self-reported male sexual disorders. There is an overlap among men with PE and those trying to achieve a pregnancy, and Promescent is a commonly used topical treatment for PE. Although there was no difference in SDF between the 2 groups, Promescent had a cytotoxic impact on sperm.

Incidence of ovarian endometrioma among women with peritoneal endometriosis with and without a history of hormonal contraceptive use.

OBJECTIVE(S): To determine if, among women with peritoneal endometriosis, the incidence of ovarian endometrioma at first laparoscopy differs between those with and without a history of hormonal contraceptive use. STUDY DESIGN: Retrospective case-control study of women who were patients at a fertility center and had first laparoscopy from 2009 through 2015 showing, at minimum, evidence of peritoneal endometriosis (n=136). Chart review was conducted for history of prior birth control use as well as operative and pathology notes of surgeries. Study subjects were grouped as follows: women with peritoneal endometriosis diagnosed by laparoscopy who had a history of hormonal contraceptive use (n=93) and women with peritoneal endometriosis diagnosed by laparoscopy who had never used hormonal contraceptives (n=43). The main outcome measure was the incidence of ovarian endometrioma among women with peritoneal endometriosis who had a history of hormonal contraceptive use as compared to women with peritoneal endometriosis who had a history of no hormonal contraceptive use. RESULTS: Among women with peritoneal endometriosis who had a history of hormonal contraceptive use, 17/93 (18.3%) were found to have endometriomas. Among women with peritoneal endometriosis who had a history of no hormonal contraceptive use, 21/43 (48.8%) were found to have endometriomas. The chi-square statistic was 13.6 (P-value<0.001). CONCLUSION(S): Among women with peritoneal endometriosis, those with a history of hormonal contraceptive use had a lower incidence of ovarian endometrioma than those with a history of no hormonal contraceptive use. Possible mechanisms of action include reducing the risk of a corpus luteum formation and subsequent transformation into an ovarian endometrioma or reducing the risk of ectopic endometrium implantation into the ovary via the diminution of retrograde menstruation. Although larger, prospective studies are needed, the findings of this study suggest that the use of hormonal contraception may decrease the likelihood of ovarian endometrioma formation among women with peritoneal endometriosis.