Comment on "Comparative Efficacy of Varicocelectomy and Intrauterine Insemination in Varicocoele Patients With Mild Semen Abnormalities: An Observational Study".

BackgroundVaricocoele is a common cause of male infertility, affecting spermatogenesis through increased testicular temperature, venous stasis, and oxidative stress. Microsurgical subinguinal varicocelectomy improves semen quality, whereas intrauterine insemination is widely used for mild male factor infertility. The comparative efficacy of these treatments in varicocoele patients with mild semen abnormalities remains unclear.ObjectivesTo evaluate the efficacy of microsurgical subinguinal varicocelectomy and intrauterine insemination in improving clinical pregnancy and live birth rates in varicocoele patients with mild semen abnormalities and assess post‐operative improvements in semen parameters following microsurgical subinguinal varicocelectomy.Materials and methodsA retrospective cohort study involving 650 microsurgical subinguinal varicocelectomy patients from five medical centers and 700 intrauterine insemination patients from one center was conducted. Inclusion criteria included varicocoele diagnosed via ultrasonography, mild semen abnormalities (total motile sperm count ≥5 million), and at least one abnormal semen parameter. Primary outcomes were clinical pregnancy and live birth rates. Secondary outcomes included sperm concentration, motility, and total motile sperm count changes post‐microsurgical subinguinal varicocelectomy. Statistical analyses included chi‐square tests and logistic regression.ResultsMicrosurgical subinguinal varicocelectomy patients demonstrated significant improvements in sperm concentration (35.2–43.3 × 10⁶/mL), motility (26%–38%), and total motile sperm count (18.8–34.9 × 10⁶, p < 0.001). Clinical pregnancy and live birth rates were higher in the microsurgical subinguinal varicocelectomy group (35.23% and 31.08%) compared to the intrauterine insemination group (29.57% and 24.00%, p < 0.05). Multivariate analysis revealed that microsurgical subinguinal varicocelectomy significantly increased pregnancy (OR = 1.43, 95% CI: 1.12–1.83, p < 0.05) and live birth rates (OR = 1.56, 95% CI: 1.21–2.02, p < 0.05).Discussion and conclusionMicrosurgical subinguinal varicocelectomy significantly enhances semen quality and achieves superior clinical pregnancy and live birth rates compared to intrauterine insemination for varicocoele patients with mild semen abnormalities. These findings suggest that microsurgical subinguinal varicocelectomy is a more effective treatment option, highlighting the importance of individualized treatment strategies and supporting the preferential use of surgical intervention in this specific patient population.

Background:Assisted human reproduction (AHR) can be used to help individuals and couples overcome infertility issues. We sought to describe trends in pregnancies using AHR and to evaluate the impact of AHR on perinatal outcomes in a large population-based cohort in Alberta, Canada.Methods:We linked maternal and child administrative data for all live births occurring July 1, 2009, to Dec. 31, 2018, in Alberta, Canada, for this retrospective study. We identified AHR pregnancies from pharmaceutical claims or codes from the International Classification of Diseases and Related Health Problems (9th or 10th revision). Our main outcome measures were the incidence and temporal trends of live births in AHR pregnancies. We also compared maternal characteristics and perinatal outcomes of AHR and non-AHR pregnancies, and by maternal age group.Results:Of 518 293 live births during the study period, 26 270 (5.1%) were conceived with AHR. The incidence of AHR pregnancies increased from 30.8 per 1000 pregnancies in 2009 to 54.7 per 1000 pregnancies in 2018. Females who used AHR were older (33.9 yr v. 30.1 yr, p < 0.001) and the number of females aged 30–35 years and older than 35 years who delivered following AHR increased over the study period (30–35 yr: 36.9 to 55.3 per 1000 pregnancies; > 35 yr: 79.1 to 95.2 per 1000 pregnancies). The proportion of live births with cesarean delivery (40.5% v. 23.3%, p < 0.001), low birth weight (26.9% v. 7.6%, p < 0.001), congenital malformation (0.5% v. 0.3%, p = 0.002) and admission to the neonatal intensive care unit (25.3% v. 9.7%, p < 0.001) was higher in the AHR group than the non-AHR group.Interpretation:The incidence of live births following AHR pregnancies in Alberta was 5.1% between 2009 and 2018, and increased by 0.26% per year; newborns in the AHR group appeared smaller and showed signs of poorer health. This study provides insights on potential perinatal complications following AHR that may be important when caring for the newborn child.

Does feeding extruded linseed to dairy cows improve reproductive performance in dairy herds? An observational study

ObjectiveTo compare success rates, associated risks and cost-effectiveness between intrauterine insemination (IUI) and in vitro fertilisation (IVF).DesignRetrospective observational study.SettingThe UK from 2012 to 2016.ParticipantsData from Human Fertilisation and Embryology Authority’s...

Study question What is the site- and morphology-specific cancer risk in a population-based Australian cohort of women who used medically assisted reproduction (MAR) between 1991 and 2019? Summary answer All-cancer risk for women who used MAR was similar to the general population. Risks for specific hormone-sensitive cancers (uterine, ovarian, melanoma) were elevated. What is known already It is biologically plausible that MAR therapies (including invasive treatments like IVF, and non-invasive treatments like ovulation induction or intra-uterine insemination) may be carcinogenic, both due to the treatment medicines used and other aspects of the treatment, such as the repeated puncture of the ovaries. Some population-based studies have suggested that risk for certain hormone-sensitive cancers may be elevated in women who have undergone MAR, particularly ovarian, uterine, and in-situ breast cancers. However, evidence is mixed, with most meta-analyses of population-studies suggesting mildly or no elevated risks in women having undergoing MAR. Study design, size, duration The current study aimed to compare the rates of cancer for women who used MAR to the general population. We used a retrospective population-based cohort design, including 430,472 women in Australia who used MAR between 1991 and 2018. We compared this cohort to the general population of women in Australia during this timeframe. Participants/materials, setting, methods We calculated the site- and morphology-specific cancer incidence rates for women who received MAR and compared these with the general population using standardised incidence ratios (SIRs), standardising by age group, state, and calendar year. We analysed invasive therapies (IVF, ICSI), and non-invasive therapies (ovulation induction, intrauterine insemination) identified through public health insurance claims. We also separately analysed those given Clomid prescriptions identified from public medicine subsidy payments. Main results and the role of chance We identified 274,145 women exposed to at least one invasive treatment, 120,555 exposed to a non-invasive treatment, and 175,468 who fulfilled a Clomid prescription. We found a comparable risk of cancer for women exposed to invasive treatments (SIR 0.98, 95%CI 0.96-1.00) or Clomid (SIR 1.02, 0.99-1.06), and slightly reduced all-cancer risk for women exposed to non-invasive treatments (SIR 0.97, 0.94-1.00). Analysis of specific cancer subtypes indicated uterine cancers (SIRs 1.23-1.83) and both in-situ and invasive melanoma (SIRs 1.07-1.19) were moderately elevated for all types of treatment, while cervical cancer (SIRs 0.52-0.61) and cancer of the trachea, bronchus, and lung (SIRs 0.61-0.70) risk was lower for all treatments. Ovarian cancer risk was elevated for invasive treatments (SIR 1.23, 95%CI 1.10-1.37) and non-invasive treatments (SIR 1.18, 95%CI 1.01-1.37). In-situ breast cancer risk was elevated only for invasive treatments (invasive: SIR 1.24, 95%CI 1.12-1.38; non-invasive: SIR 1.14, 95%CI 0.96-1.34). Clomid prescriptions showed no increased risk for either (ovarian: SIR 1.00, 95%CI 0.82-1.21; in-situ breast: SIR 1.05, 95%CI 0.92-1.19). We found evidence that non-melanoma skin (SIRs 1.86-2.96), non-trachea, bronchus, and lung respiratory cancers (SIRs 2.11-2.78) were elevated, but these findings would be prone type 1 error due to small numbers of observed cancers (&amp;lt;30). Limitations, reasons for caution Though we describe an elevated risk of some cancers following MAR, these results should not be interpreted as a causal effect. There are many potentially confounding factors (such as cause of infertility, parity, smoking history) for which we could not control due to the nature of the dataset. Wider implications of the findings Though certain cancers may be elevated in women who underwent MAR, there is no evidence these women are more at risk of cancer generally than the general population. Clinicians should be aware that certain hormone-sensitive cancers may be more likely in women who undertake MAR. Trial registration number No

Our objective was to investigate associations of postpartum health with serum progesterone (P4) concentrations after first artificial insemination (AI), expression of interferon-stimulated genes (ISG) in blood leukocytes, and serum pregnancy-associated glycoprotein (PAG) during early pregnancy in dairy cows. In this observational study, Holstein cows (n = 475) from 2 commercial herds were enrolled 3 wk before expected parturition. Body condition score (BCS) and lameness were assessed at enrollment, and total Ca, haptoglobin, and nonesterified fatty acids (NEFA) were measured in serum at 2 and 6 ± 2 d in milk (DIM). Blood β-hydroxybutyrate and metritis were evaluated at 4, 8, 11, and 15 ± 2 DIM, and purulent vaginal discharge (PVD) and endometritis based on endometrial cytology were diagnosed at 35 DIM. Onset of cyclicity was assessed by biweekly P4 measurements. The BCS was assessed at enrollment and at 63 DIM, and lameness at enrollment and at 21 and 49 DIM. First AI was based on estrus detection until ∼75 DIM, or synchronization for timed AI thereafter. Serum P4 was measured at d 8 and 12 after first AI; expression of ISG (ISG15 and RTP4) in blood leukocytes was assessed at d 19; and PAG in serum of pregnant cows was measured at d 29, 33, and 40. Multivariable linear regression models were built including health variables (with metabolites categorized via receiver operating characteristic curve analysis) and covariates (season, milk yield, AI method, DIM), accounting for pregnancy status (for ISG and PAG models), repeated measures (for P4 and PAG models), and herd as random. Results are reported comparing cows affected versus unaffected by each predictor. Serum P4 concentrations were lesser at d 8 after AI in cows that had total Ca ≤2.09 mM (3.6 vs. 4.0 ± 0.2 ng/mL) at 2 DIM or a clinical disease (3.7 vs. 4.0 ± 0.2 mg/mL), and P4 tended to be lesser at d 8 in cows that had PVD (3.6 vs. 4.0 ± 0.2 ng/mL) or any uterine disease (3.7 vs. 4.1 ± 0.2 ng/mL). Among cows pregnant at d 29, relative ISG15 expression (fold change) at d 19 was greater in cows that had lameness (5.10 [4.18-6.18] vs. 3.14 [3.10-3.19]) but tended to be lesser in cows that had endometritis (3.20 [2.89-3.54] vs. 4.29 [4.20-4.35]), and relative expression of RTP4 tended to be lesser in cows that had displaced abomasum (1.02 [0.62-1.67] vs. 1.75 [1.73-1.78]). Serum PAG was lesser at d 29 (3.8 vs. 4.2 ± 0.2 sample-to-positive ratio [S:P]) in cows that had NEFA ≥0.73 mM at 6 DIM, and lesser at d 33 (3.9 vs. 4.5 ± 0.2 S:P) and 40 (3.1 vs. 3.7 ± 0.2 S:P) in cows that had prepartum BCS ≥3.75. These findings suggest long-term effects of metabolic or reproductive tract disorders on luteal function after first AI, pregnancy recognition signaling, and placental function during early pregnancy. These associations may partially explain some of the pathways linking postpartum health and fertility in dairy cows.

Objective: The aim of this study is the comparison of effects of Clomiphene Citrate (CC) & human menopausal Gonadotrophin (hMG) stimulated cycles on the Endometrial Thickness (ET) in intrauterine insemination (IUI) in one cycle & to establish any relation between ET on the day of IUI and achieving clinical pregnancy in these stimulated cycle.Study design: A prospective observational study was undertaken for assessing effects of clomiphene citrate (CC) and human menopausal gonadotrophin hMG stimulated cycle on the ET and clinical pregnancy in single IUI cycle.Subfertility cases were studied in two groups; Group A [ovulation induction (OI) with CC and IUI, n = 150] and Group B (OI with hMG and IUI, n = 150).Results: Comparable data obtained in mean, age, duration of subfertility female, male (only oligo sperm a) in both group range of ET of clinical pregnancy in group A (n = 21) were 8.0 – 12.9 mm and 9.0 – 12.9 mm in group B (n = 40). (p value < 0.001) ongoing pregnancy beyond 1st trimester was higher in group B (n= 42) than group A (n = 19).Conclusion: Mean ET and clinical pregnancy rate both were higher in hMG group compared to CC.

Effectiveness and safety of intrauterine insemination vs. assisted reproductive technology: emulating a target trial using an observational database of administrative claims

Study question Can SDF assessment pre-cryopreservation, post-thaw and after post-thaw sperm selection predict clinical outcome in a heterologous intra-uterine donor insemination program (IUI)? Summary answer SDF increased post-cryopreservation in donor sperm and after post-thaw density gradient without affecting clinical pregnancy, live birth and miscarriage rates. What is known already Sperm cryopreservation is effective for preservation of male fertility and facilitates the storage of donor semen, while infectious disease screening can be completed and confirmed negative. Sperm viability and motility are the most vulnerable parameters during the freeze-thaw process. Inherent reactive oxygen species may induce SDF via oxidative stress. Controversial results are reported regarding induction of SDF after cryopreservation due to differences in cryo tolerance, methods of cryopreservation and methods used to evaluate SDF. Sperm selection post-thaw is indispensable to select a normal motile fraction for insemination. Again, results are controversial regarding influence on SDF levels after sperm selection post-thaw. Study design, size, duration This was a prospective, observational study. Between March 2015 and March 2019, eighteen potential sperm donors were screened via a three step plan – semen assessment, medical assessment and serological blood tests. In accordance with the Belgian legislation (2007), a sperm donor was matched to obtain a maximum of 6 pregnancies in acceptor women/couples, allowing for more than one offspring/woman or couple. A total of 106 acceptors were matched for heterologous intra-uterine insemination. Participants/materials, setting, methods Semen samples were collected after 2-7 days abstinence and standard semen parameters analyzed within 60 mins after ejaculation. Within the same time frame SDF test was performed using TUNEL assay both before and after cryopreservation and after a two-step discontinuous density gradient centrifugation post-thaw. Samples were cryopreserved by the conventional slow freezing method using sperm freeze solution. A yield of ≥ 2 M progressive spermatozoa post-thaw after selection was sufficient to contemplate IUI. Main results and the role of chance Mean female age at first cycle was 33.9 ± 4.1 years and donor age 28.5 ± 5.6 years. Out of 429 cycles, 100 (23.3%) resulted in clinical pregnancy. Excluding three ongoing pregnancies, we counted 75 live births (17.6% of cycles or 77.3% of pregnancies), while 21 pregnancies ended in miscarriage (4.9% of cycles or 21.6% of pregnancies) and 1 resulted in stillbirth. Progressive motility (59.3 ± 12.5%) decreased significantly after cryopreservation (30.0 ± 13.2%; p &amp;lt; 0.001), but increased post-thaw after density gradient centrifugation (61.6 ± 16.0%; p &amp;lt; 0.001). On the contrary, SDF (12.0 ± 5.9%) increased post-cryopreservation (26.3 ± 14.5%; p &amp;lt; 0.001) and further increased after sperm selection (34.9 ± 22.1%; p = 0.04). Using multilevel mixed-effects logistic regression (Odds ratio [95%CI]), we found that female age significantly influenced clinical pregnancy (0.911 [0.847-0.981]; p = 0.01), live birth (0.894 [0.834-0.959]; p = 0.002) and miscarriage rates (1.180 [1.033-1.347]; p = 0.015). There was no significant age-adjusted effect of SDF post-thaw after density gradient selection on clinical pregnancy (1.007 [0.994-1.021]; p = 0.30), live birth (1.001 [0.988-1.014]; p = 0.84) or miscarriage (1.021 [0.997-1.046]; p = 0.08). Median time-to-live birth was 4 cycles. Analyses of time-to-live birth with mixed-effects Cox models revealed no significant association with progressive motility; SDF before or after cryopreservation and after sperm selection post-thaw. Limitations, reasons for caution Results concern a small donor population, with high normal semen parameters and should therefore be extrapolated cautiously to subfertile men with normal and subnormal semen parameters. Wider implications of the findings In a donor IUI program with strict selection on conventional sperm parameters, differences in SDF before and after cryopreservation and gradient centrifugation do not change IUI outcomes, although cryopreservation and centrifugation increase SDF. Findings could be useful for the optimization of sperm freezing and selection in different assisted reproductive procedures. Trial registration number not applicable

Study question If we have a woman with a poor ovarian reserve, will she have a lower chance of pregnancy after a cycle of IUI? Summary answer A woman with a poor ovarian reserve has a lower chance of pregnancy, although in donor IUI we have an acceptable rate of pregnancy. What is known already Actually, the better predictor to define a poor ovarian reserve is a low antimullerian hormone (AMH). AMH is a well-known predictor of ovarian reserve, which allow to predict a response after an in vitro fecundation (IVF) cycle. Nevertheless, we also know that a low AMH does not mean to be not able to get pregnant. Few studies have compared different markers of ovarian reserve as predictors of pregnancy after an IUI cycle, and those which have done it have conflictive results. Maternal age seems to be strongly linked with the chance of pregnancy. Study design, size, duration We designed a retrospective cohort study with longitudinal follow-up upon the patients who undergo an IUI cycle in a public hospital of third level (Hospital Virgen del Rocio, Seville, Spain). We included 1059 cycles of IUI (383 with conjugal and 676 with donor semen) between 2015 and 2021. These cycles belong to 390 patients (64 with poor ovarian reserve and 326 with normal ovarian reserve). Participants/materials, setting, methods We collected data from clinical history which is completed during the visit of the patients. Cohort was stratified between patients with a low AMH (&amp;lt;1.1 ng/ml) and normal AMH (&amp;gt;1.1 ng/ml). We used this cut point following the definition of our regional guideline that includes when we can practice fertility treatments. Our main variable was pregnancy rate, defining pregnancy as an echography at 7 weeks with at least one embryo with cardiac activity. Main results and the role of chance When we compared pregnancy rate between normal ovarian reserve against poor ovarian reserve, we did not find statistically significant results in conjugal IUI independently that we compared by cycle (11.2% in normal ovarian reserve vs 3.8% in poor reserve (p = 0.2)) or by couple (27.97% in normal ovarian reserve vs 8.3% in poor ovarian reserve (p = 0.1)). We found differences with the same comparison in donor IUI by cycle (20.2% normal reserve vs 6.8% in poor reserve (p = 0.001)) and by couple (56.83% in normal ovarian reserve vs 21.15% in poor reserve (p = 0.001)). Nevertheless, pregnancy rate in IUI was similar to what we will get with an IVF cycle with only one oocyte. We compared pregnancy rate between normal ovarian reserve patients who undergo a conjugal IUI cycle, with low reserve patients who undergo a donor IUI cycle. When we compared by cycle normal ovarian reserve patients had 11.2% pregnancy rate, while poor ovarian reserve patients had a 6.8% (p = 0.1). When we compared by couple normal ovarian reserve patients had a pregnancy rate of 27.97% while poor ovarian reserve patients had a 21.15% (p = 0.3). Actually, our regional guide excludes poor ovarian reserve woman of an IVF cycle in the public system. Limitations, reasons for caution We had the proper limitations of an observational retrospective study. As we are a public center, we must follow our regional guide which defines whether we can do a treatment or not. Wider implications of the findings Patients with a poor ovarian reserve have a lower pregnancy rate during IUI with donor semen. Nevertheless, this rate could be acceptable especially when we cannot offer them an IVF cycle in public healthcare. Trial registration number Not applicable

The objective of this study was to compare pregnancy outcomes resulting from artificial insemination (AI) with multi-sire semen (MS) compared with single-sire semen (SS) in beef heifers. Another study observed pregnancy and paternity outcomes to sexed MS without a control treatment. In the first study, unrelated ABS Global Angus bulls (n = 3) were selected for AI to 441 (Yr 1) and 391 (Yr 2) Angus crossbred heifers. Heifers were synchronized with the melengestrol acetate – prostaglandin F2α timed-AI protocol. Conventional semen, from each bull, were labeled A, B, or C. Remaining semen was pooled in equal amounts to form conventional MS straws. Heifers were AI using alternating treatment of MS or SS: A, B, or C with one-half of inseminated heifers receiving either MS or SS. The GLIMMIX procedure in SAS 9.4 analyzed responses to treatments using the BIN distribution option and reported as LSMEANS. Contrasts and estimates analyzed responses between treatments. Ultrasound determined SS pregnancy rate averaged 60% (SS-A = 64%, SS-B = 58%, SS-C = 58%) and MS average 62% (P = 0.63). Paternity was determined in 57 MS calves and confirmed in 49 SS calves. In Yr 1, Bull A sired 7%, bull B sired 56%, and bull C sired 37%. Although bull A was much less successful than bull B or C, the values are not significantly different due to the small sample size (P = 0.11 and P = 0.24, respectively). Few conclusions can be made from the ongoing study, but it is hypothesized MS may improve consistency of pregnancy rate by equilibrating semen quality in herds subjected to timed AI. In the observational study, multiple 5-way cross bulls born from the ranch herd were selected for AI of 951 ± 41 heifers for 3 yr. Heifers were synchronized using the previously mentioned protocol with split-time AI. Unequal amounts of semen were collected, pooled, and sexed to favor heifer progeny at an expected ratio of 9:1. Semen from 2 to 4 random bulls were pooled making 3 to 4 MS groups each year. Heifers exhibiting estrus were administered sexed MS, but there was no control treatment. The observed ultrasound determined average pregnancy rate of heifers administered sexed MS was 65% (Yr 1), 75% (Yr 2), and 72% (Yr 3). Previous literature suggests average pregnancy rate to AI with sexed SS is 53%. Paternity testing in Yr 2 found semen contribution mirrored paternity ratios within some groups but the sire group with 2 bulls found one sired 15% and the other sired 85%. This study exemplified a viable method for AI that requires further research. Further research into semen quality of a single sire, and pooled semen could lead to optimization of fertilization among individuals within a herd.

Estrous detection intensity and accuracy and optimal timing of insemination with automated activity monitors for dairy cows

Equine reproduction (1993)

The objective of this study was to characterize the associations between body condition score (BCS) and BCS change (∆BCS), determined by an automated camera system during early lactation and close to artificial insemination (AI), and the subsequent pregnancy loss (PL) in Holstein cows. A secondary objective was to determine the impact of disease on PL, considering multiple time periods relative to AI. Data from 9,430 lactations in 6,884 Holstein cows in a commercial dairy operation located in Colorado, USA were included in this retrospective observational study. Cows were subject to first AI at about 80 DIM (primiparous) and 60 DIM (multiparous), following a double OvSynch protocol. Pregnancy diagnosis was performed via transrectal ultrasonography on day 32 ± 3 after AI and reconfirmed on day 80 ± 3 after AI. Cameras mounted on the sorting gate at each exit (n = 2) of the milking parlor generated BCS on a five-point scale with 0.1 increments. The BCS at calving (BCS1), 21 DIM (BCS21), 56 DIM (BCS56), AI resulting in pregnancy (BCSAI), and 90 d post AI (BCSAI90) were selected for the analyses and subsequently categorized as low (≤ lower quartile), moderate (interquartile range), and high (≥ upper quartile). Changes in BCS were calculated by periods of interest as change from calving to 21 DIM; change from calving to 56 DIM; change from 56 DIM to AI; and change from AI to 90 d post AI and assigned into categories to facilitate the analysis. Data were examined using logistic regression, considering parity category, season at calving and AI, DIM at AI, milk yield up to 60 DIM, and occurrence of disease as covariables. The logistic regression analyses indicated that the odds of PL were greater in cows in the low BCS category relative to cows in the high BCS category at 56 DIM (OR 95% CI = 1.41 [1.12-1.79]), AI (1.31 [1.05-1.65]), and 90 d post AI (1.38 [1.10-1.74]). Likewise, cows with large loss in BCS between calving and 21 DIM (1.46 [1.10-1.94]) and loss in BCS between AI and 90 d post AI (1.44 [1.15-1.81]) had greater odds of PL compared with cows with no loss of BCS within the same period. Occurrence of disease at all the time periods considered in the analysis had a consistent detrimental impact on maintenance of the pregnancy, supporting the concept that pre and postconceptional disease affects embryonic survival. Overall, low BCS, more pronounced reductions in BCS occurring closer to AI, and occurrence of disease resulted in greater PL in this Holstein population.

The Effects of Time of Disease Occurrence, Milk Yield, and Body Condition on Fertility of Dairy Cows