Does sperm retrieval increase cost without benefit for men with non-obstructive azoospermia? A cost-effectiveness analysis of sperm retrieval vs. donor sperm

We are thankful to Dr. Drobnis for her insights and balanced comments with regard to our article titled “comparison of sperm retrieval and reproductive outcome in azoospermic men with testicular failure and obstructive azoospermia treated for infertility”.1 Our main objective was to offer firm information that could be used as a counseling tool by doctors treating patients with azoospermia-related infertility. The key message was that non-obstructive azoospermia (NOA) negatively affect the success rates of both surgical sperm retrieval and live birth rates after intracytoplasmic sperm injection (ICSI), by approximately halving their results, but not the neonatal outcomes of the resulting offspring, when compared with obstructive azoospermia (OA). To achieve this conclusion, we compared sperm retrieval rates (SRR), ICSI outcomes and the neonatal profile of babies born in men with NOA and OA, after controlling for covariates that could potentially bias the results. We used microdissection testicular sperm extraction (micro-TESE) as a sperm acquisition method in our group of men with NOA to offer them the best possible chance of having sperm retrieved. For comparison, we included a subgroup of couples treated by ICSI with donor sperm due to failed micro-TESE. Interestingly, the magnitude of the aforementioned negative effects was also similar when NOA was compared with donor sperm, albeit not different between OA and donor sperm. We agree with Dr. Drobnis that we could have added the outcomes in NOA according to the patients’ testicular biopsy results and separately for men with Klinefelter syndrome (KS), owed to the limited information available in the literature for these subsets of patients. As far as KS is concerned, our dataset comprised eight men with KS, of whom four had sperm retrieved by micro-TESE and used for ICSI. Two pregnancies were obtained after ICSI using testicular sperm from KS patients, of which one resulted in a miscarriage at the 11-week gestation while the other in a delivery of health preterm twins at the 35 gestational week. We present SRR, ICSI outcomes and the profile of neonates born according to the patients’ testicular biopsy results (Table 1). Patients with maturation arrest (MA) had lower SRR compared with those with sertoli-cell only (SCO) (P = 0.007). Both categories had lower SRR compared with hypospermatogeneis (P < 0.001). Live birth rates were lower in SCO compared with both hypospermatogenesis and MA after adjusting for covariates (P = 0.01), whereas the obstetrical outcomes of resulting offspring were not affected by the testicular histopathology categories. Our data indicate that SRR and live birth with ICSI are differentially affected by the severity of disruptive spermatogenesis in men with NOA. Nevertheless, the neonatal profile of resulting offspring was not affected by the severity of testicular failure.Table 1: SRR, live birth and obstetrical outcome of resulted offspring according to testicular histology results in patients with non-obstructive azoospermiaAlthough our data indicate that the biopsy results have prognostic value for the chances of SR and live birth, we do not recommend routine testicular biopsy prior to sperm retrieval in men with NOA. An advanced site of sperm production can be found even in the worst case scenario of SCO.23 Moreover, removal of testicular tissue with the sole purpose of histopathological evaluation could potentially remove foci of sperm production and thus jeopardize the chances of future successful retrieval attempts.4 Our routine is to take a small testicular biopsy specimen during sperm retrieval for histologic confirmation of NOA. COMPETING INTERESTS The authors declare no competing interests.

Assisted reproductive technology with donor sperm: national trends and perinatal outcomes

Assisted reproductive technology with donor sperm: national trends and perinatal outcomes

Report on management of obstructive azoospermia

PMS19 A SYSTEMATIC REVIEW OF ECONOMIC MODELS FOR COST EFFECTIVENESS OF PHYSIOTHERAPY INTERVENTION FOLLOWING TOTAL KNEE AND HIP REPLACEMENT

P-629: Assisted reproductive treatments versus unprotected intercourse to achieve pregnancy for HIV serodiscordant couples: A cost-effectiveness analysis

In vitro fertilization with preimplantation genetic testing compared with donor sperm and natural conception among male Robertsonian translocation carriers: a cost-effectiveness analysis

To examine the cost-effectiveness of semi-rigid ankle brace to facilitate return to work following first-time acute ankle sprains. Economic evaluation based on cost-utility analysis. Ankle sprains are a source of morbidity and absenteeism from work, accounting for 15-20% of all sports injuries. Semi-rigid ankle brace and taping are functional treatment interventions used by Musculoskeletal Physiotherapists and Nurses to facilitate return to work following acute ankle sprains. A decision model analysis, based on cost-utility analysis from the perspective of National Health Service was used. The primary outcomes measure was incremental cost-effectiveness ratio, based on quality-adjusted life years. Costs and quality of life data were derived from published literature, while model clinical probabilities were sourced from Musculoskeletal Physiotherapists. The cost and quality adjusted life years gained using semi-rigid ankle brace was £184 and 0.72 respectively. However, the cost and quality adjusted life years gained following taping was £155 and 0.61 respectively. The incremental cost-effectiveness ratio for the semi-rigid brace was £263 per quality adjusted life year. Probabilistic sensitivity analysis showed that ankle brace provided the highest net-benefit, hence the preferred option. Taping is a cheaper intervention compared with ankle brace to facilitate return to work following first-time ankle sprains. However, the incremental cost-effectiveness ratio observed for ankle brace was less than the National Institute for Health and Care Excellence threshold and the intervention had a higher net-benefit, suggesting that it is a cost-effective intervention. Decision-makers may be willing to pay £263 for an additional gain in quality adjusted life year. The findings of this economic evaluation provide justification for the use of semi-rigid ankle brace by Musculoskeletal Physiotherapists and Nurses to facilitate return to work in individuals with first-time ankle sprains.

Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction

Are the early pregnancy outcomes of IVF pregnancies conceived with donor sperm different to those conceived with partner sperm? Pregnancies conceived with donor sperm have a lower odds of early pregnancy loss and ectopic pregnancy compared to pregnancies conceived with partner sperm. The number of cycles using donor sperm has risen significantly in recent years. Adverse early pregnancy outcomes have a negative impact on women and their partners. The evidence available to date regarding early pregnancy outcomes for pregnancies conceived with IVF donor sperm is limited by low numbers and lower-quality studies. This is a retrospective cohort study of 1376454 cycles conceived with either donor or partner sperm between 1991 and 2016 as recorded in the Human Fertilisation and Embryology Authority (HFEA) Register. The HFEA has recorded data on all fertility treatments carried out in the UK from 1991 onwards, and it publishes this data in an anonymized form. This study assessed the outcomes of all pregnancies conceived with donor sperm and compared them to those conceived with partner sperm among IVF cycles recorded in the HFEA anonymized dataset from 1991 to 2016. Cycles that included intrauterine insemination, donor oocytes, preimplantation genetic testing, oocyte thaw cycles and alternative fertility treatments were excluded. The outcomes of interest were biochemical pregnancy, miscarriage, ectopic pregnancy, stillbirth and live birth. Logistic regression was used to adjust for confounding factors including age of the female partner, cause of infertility, history of previous pregnancy, fresh or frozen cycle, IVF or ICSI, number of embryos transferred, and year of treatment. Results are reported as adjusted odds ratios (aOR) and 95% CIs. This study found reductions in the odds of biochemical pregnancy (aOR 0.82, 95% CI 0.78-0.86), miscarriage (aOR 0.93, 95% CI 0.89-0.97), and ectopic pregnancy (aOR 0.77, 95% CI 0.66-0.90) among pregnancies as a result of the use of donor sperm as opposed to partner sperm. This study is retrospective and limited by the constraints of routinely collected data. No data were available for maternal characteristics such as BMI, smoking and partner age, which could all be potential confounders. Clustering of multiple pregnancies within women could not be accounted for as the data are reported only at the cycle level with no maternal identifiers. This study has demonstrated that there are no increased risks of adverse pregnancy outcome with donor sperm pregnancies. The reduction in miscarriage in pregnancies using donor sperm suggests that sperm could have a role in miscarriage, as the selection process for being accepted as donor is stringent. No external funding was sought for this study. C.A. has received funding from Ferring to attend a UK meeting for trainees in reproductive Medicine. A.M. has received funding from Ferring, Cook, Merck Serono, Geodon Ritcher, and Pharmasure for speaking at, or attending, meetings relating to reproductive medicine. She has also participated in a Ferring advisory board. S.B. has received grants from Tenovus and the UK Medical Research Council. She has also been supported with a Medical Research Scotland PhD studentship. N/A.

Study question Does the sperm retrieved surgically by MD-TESE of men with Non-Obstructive Azoospermia affect the live birth sex ratio? Summary answer Our data indicates that sperm retrieved in men with non-obstructive azoospermia alters the sex ratio in favor of female offspring. What is known already Non-Obstructive Azoospermia is the most severe form of male infertility and is the most common cause of Azoospermia. Among the different surgical techniques, MD-TESE gives the highest rate of sperm retrieval and when combined with intracytoplasmic sperm injection (ICSI), live births had been achieved with variable success, Sex ratio of offspring can vary substantially due to several variables, however no studies have investigated the resultant birth sex ratio in this setting. Study design, size, duration Retrospective Cohort study. Data were collected between May 2009 and December 2019. A total of 100 consecutive men with non-obstructive Azoospermia underwent MD-TESE for sperm retrieval. 46 couples underwent ICSI and live birth rate, cumulative live birth rate and sex ratio of offspring analysed. Participants/materials, setting, methods One-hundred men underwent MD-TESE out of which 46 proceeded with ICSI. Demographic data including male and female age, testicular volumes and serum hormone values are given as mean ± SD with a range (minimum and maximum). Fertility outcomes including sperm retrieval, fertilization rate, number of embryos transferred, and live birth rates and cumulative live birth rates were recorded. Chi-square test was performed to compare the proportions. Main results and the role of chance Sperm retrieval was successful in 58%(58/100). Testicular volume and hormonal parameters did not vary among patients with positive or negative sperm retrieval. Histology gave best correlation with sperm retrieval. Hypospermatogenesis yielded the highest sperm retrieval 93%(26/29), followed by Maturation arrest 78%(7/9), then Hyalinosis 46% (6/13) and lastly Sertoli cell only 38%(19/50). 46 couples underwent ICSI cycles where the mean age of patients and their wives were 36.4 ± 3.7y and 33.0 ± 4.3y. Fertilization rate and mean number of transferred embryos were 51.4 % and 1.7. Live birth rate and Cumulative Live Birth rate per Embryo transfer were 60.5% (26/43) and 74.4% (32/43) and per started ICSI cycle were 56.5% (26/46) and 69.6% (32/46), with a twin rate of 15.3%(4/26). Mean gestational length and mean body weight at birth were 39.0 ± 1.4w and 3228.5 ± 5.5 g. Number of live offspring were 36 (Female: Male = 26:10) giving rise to sex ratio of 2.6 to1 in favor of female offspring (P &amp;lt; 0.05). There were no neonatal death, and one baby had phenylketonuria. Limitations, reasons for caution This is the first study to test the hypothesis of sex ratio variation related to the source of sperm; the strength of our study is that all procedures were performed by the same surgeon, so there are no operator-dependent differences. This finding needs to be confirmed in larger cohort studies. Wider implications of the findings It has been demonstrated that different stressors may alter the sex of the offspring. While in the present study the stressor is the parental hypogonadism associated with non-obstructive azoospermia, We hypothesise that testicular environment may direct spermatogenesis in favor of X carrying sperm around the time of sperm retrieval. Trial registration number N/A

Study question Are perinatal outcomes different in pregnancies conceived using donor sperm compared with those with partner sperm? Summary answer The perinatal outcomes of singleton and twin pregnancies conceived with donor sperm are better when compared to those conceived with partner sperm What is known already There has been a substantial increase in the use of donor sperm in the last 15 years across the world. A recent systematic review and meta-analysis has suggested that there is an increased risk of hypertensive disorders of pregnancy and small for gestational age babies from ART treatment using donor sperm compared to partner`s sperm. This meta-analysis was limited due to poor quality of primary studies often with small sample sizes. Study design, size, duration This is a retrospective cohort study on 196,293 singleton and 46,275 twin pregnancies from the Human Fertilisation and Embryology Authority (HFEA) anonymised dataset including all live births from 1991 to 2016. Outcomes were preterm birth ( &amp;lt; 37 weeks); very preterm birth ( &amp;lt; 32 weeks); very low, low, high and very high birth weight ( &amp;lt; 1500g, &amp;lt; 2500g, &amp;gt;4000g and &amp;gt;4500g respectively); congenital anomaly and healthy baby (term live birth with appropriate weight and no congenital anomaly). Participants/materials, setting, methods All pregnancies resulting in singleton or twin livebirth were included. Any cycle involving donor oocytes, PGD, gamete intra-fallopian transfer, ectopic pregnancy, miscarriage, stillbirth, or termination was excluded. Logistic regression and generalised estimating equations were used for analysis of singletons and twins, respectively. Odds ratios (aOR) with 95% confidence intervals (CI) for donor versus partner sperm were adjusted for maternal age, previous pregnancy, cause of infertility and year for all outcomes plus gestational age for birthweight. Main results and the role of chance Baseline characteristics for donor and partner sperm pregnancies were assessed for singleton and twin livebirths separately. In both analyses there were significant differences between donor and partner sperm pregnancies in terms of maternal age, previous pregnancy status and cause of infertility. Analysis of singleton births demonstrated an increased odds (aOR, 95% CI) of having a healthy baby (1.09, 1.05 - 1.12) and reduced odds of congenital anomaly (0.34, 0.29 - 0.39), very preterm birth (0.66, 0.58-0.75), preterm birth (0.81, 0.76-0.86), low birthweight 0.89 (0.83 - 0.96) in singleton births using donor sperm compared with those using partner sperm. There was, however, an increased odds of high birthweight (1.10, 1.05 - 1.16) and very high birthweight (1.16, 1.05-1.29) with donor sperm pregnancies. Analysis of twin births conceived with donor sperm also showed higher odds of having a healthy baby (1.07, 1.01 - 1.15) and lower odds of congenital anomaly (0.52, 0.39 - 0.68) compared with partner sperm. There were no statistically significant differences between the birthweight or birth gestation outcomes for twin pregnancies. Sensitivity analysis of only cases with complete outcome data showed no significant differences when compared to the primary analysis. Limitations, reasons for caution This is a retrospective study of a single nation’s routinely collected data. We could not adjust for confounders such as smoking, BMI and pregnancy complications such as pre-eclampsia, as they are not recorded in HFEA’s dataset. Wider implications of the findings Patients and clinicians can be reassured that donor sperm pregnancies are not at higher risk of adverse perinatal outcomes. In fact, they are more likely to result in a healthy baby. Worldwide registries should consider including maternal data to enable a better assessment of outcomes. Trial registration number Not applicable

Objective To assess whether revascularisation that is considered to be clinically appropriate is also cost effective.Design Prospective observational study comparing cost effectiveness of coronary artery bypass grafting, percutaneous coronary intervention,...

Background The incidence of hypoxic-ischemic encephalopathy (HIE) is 0.5 per 1,000 live births. Current standard treatment is therapeutic hypothermia (cooling) begun within 6 hours of life. In infants with severe HIE, this results in fewer deaths; however, more infants survive with major neurodevelopmental disability. Objective We sought to determine whether cooling is cost-effective compared to no cooling in cases of severe HIE, and to compare it to the cost-effectiveness of cooling in cases of moderate HIE. Study design A decision analytic model using TreeAge Pro (2020) software was designed comparing cooling to no cooling in a cohort of 5,800 term neonates with HIE. Model inputs were derived from the literature. Utilities were applied to life expectancy to generate quality-adjusted life years (QALYs). All costs and QALYs were discounted at an annual rate of 3%. The strategy was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were conducted to assess the robustness of the results. Results Cooling for the management of severe HIE resulted in increased costs and increased QALYs, with an ICER of 6,864. In our theoretical cohort, cooling resulted in 835 fewer neonatal deaths, but 52 additional cases of severe neurological disability with cooling due to increased survival. When varying the probability of a healthy child with cooling in univariate sensitivity analysis, cooling was found to be the cost-effective strategy across all ranges and the dominant (lower costs, higher QALYs) strategy above 68% (baseline estimate: 63%). Multivariate sensitivity analysis found cooling was the cost-effective strategy 99.7% of the time. Conclusion Cooling is the cost-effective intervention with improved outcomes for neonates with severe perinatal hypoxic-ischemic encephalopathy over a wide range of assumptions. Despite the increased cost, more neonates survive morbidity free when compared with no cooling.

Introduction and aims: Illicit methamphetamine (MA) use is an important public health concern. There is a dearth of knowledge about effective and cost-effective treatments for methamphetamine (MA) dependence in Australia. This article evaluates the cost-effectiveness of counselling as a treatment option for illicit MA use compared with no treatment option.Design and methods: Data are from 501 individuals recruited into Methamphetamine Treatment Evaluation Study (MATES). The population of MA users from MATES is extrapolated to a total number of 1000 MA users in the intervention group (counselling treatment) and control group (non-treatment group). A decision analytic model is developed that examines the costs and health outcomes [measures as quality adjusted life years (QALYs) gained] for the treatment and comparison group over a 3-year period. A societal perspective is adopted and model inputs are subject to sensitivity and uncertainty analysis to test the robustness of results to parameter variability. Results are discounted by using 3% discount rate and expressed in 2011 Australian dollars.Results: The incremental cost-effectiveness analysis suggests that counselling is a dominant health care intervention, i.e. saves money and is more effective than a do nothing intervention. The incremental difference in costs is −AU$18.36 million (95% CI −AU$22.80 million to −AU$14.31 million) and the incremental difference in QALY is 107 (95% CI −640 to 820) with a probability of 78.64% of counselling being a dominant and cost-effective treatment within the acceptable incremental cost-effectiveness ratio (ICER) of $63 832 per QALY in the Australian society. The results of the sensitivity analysis show that the ICER is most sensitive to change in five major inputs: baseline utility, utility at 3 months, dealing crime costs, property crime costs and fraud crime costs.Discussion and Conclusions: The economic evaluation of the cost-effectiveness of counselling for MA dependence, as a first cost-effectiveness study to assess psychosocial treatment options for MA dependence, shows that greater investment in this cost-effective strategy will produce significant cost-savings and improve health outcomes as well as improve a lot of externality issues associated with drug use.