Sperm chromatin dispersion test before sperm preparation is predictive of clinical pregnancy in cases of unexplained infertility treated with intrauterine insemination and induction with clomiphene citrate

Background/aims: A large proportion of men with normal sperm results as analyzed using conventional techniques have fragmented DNA in their spermatozoa. We performed a prospective study to examine the incidence of DNA fragmentation in sperm in cases of couples with previously unexplained infertility and treated with intrauterine insemination. We evaluated whether there was any predictive value of DNA fragmentation for pregnancy outcome in such couples. Methods: The percentage of DNA fragmentation and all classical variables to evaluate sperm before and after sperm treatment were determined. We studied the probable association between these results and pregnancy outcome in terms of clinical and ongoing pregnancy rate per started first cycle. We also assessed the optimal threshold level to diagnose DNA fragmentation in our center. Results: When using threshold levels of 20, 25, and 30%, the occurrence of DNA fragmentation was 42.9, 33.3, and 28.6%, respectively. Receiver operating characteristic (ROC) analysis of all cases revealed an area under the curve of 80% to predict the clinical pregnancy rate per cycle from testing the sperm motility (a + b) before treatment. We failed to generate an ROC curve to estimate pregnancy outcome from the amount of DNA fragmentation before treatment. However, when selecting only those men with a pretreatment DNA fragmentation of at least 20%, the pretreatment result was statistically different between couples who achieved a clinical pregnancy and those who did not. Conclusion: DNA fragmentation is often diagnosed in couples with unexplained infertility. Each center should evaluate the type of test it uses to detect DNA fragmentation in sperm and determine its own threshold values

Blastocyst transfer for all? : Higher cumulative live birth chance in a blastocyst-stage transfer policy compared to a cleavage-stage transfer policy

Background: In an unselected patient population, what is the cumulative live birth rate per oocyte collection cycle in a blastocyst-stage transfer policy compared to a cleavage-stage transfer policy? Methods: A retrospective cohort analysis of 1656 IVF and ICSI cycles was performed in two timeframes between January 2010 and December 2016. Transfer was scheduled, either on day 3 (n=729) or on day 5 (n=927). In this study, the main outcome measure was cumulative live birth rate per oocyte collection cycle including fresh and frozen embryo transfers in both groups. Results: The cumulative live birth rates per oocyte collection cycle were comparable between patients with cleavage-stage transfers (day 3 group) and those with blastocyst-stage transfers (day 5 group) (23.7% versus 25.5%, respectively; p = 0.42). After controlling for confounders, there was a 34% increased chance of live birth with blastocyst-stage transfer policy compared with cleavage-stage transfer policy (odds ratio (OR) =1.34; 95% confidence interval (CI), 1.051 to 1.704; p = 0.018). Conclusion: In an unselected patient cohort, the cumulative live birth chance per oocyte collection cycle is higher in a blastocyst-stage transfer policy compared to a cleavage-stage transfer policy

Long term effects of micro-surgical testicular sperm extraction on androgen status in patients with non obstructive azoospermia

BACKGROUND: The aim of our study was to review the results of microsurgically performed testicular sperm extraction (TESE) and to evaluate its possible long term effects on serum testosterone (T). METHODS: We operated on 48 men (35 +/- 8 years) with non-obstructive azoospermia (NOA). If no spermatozoa were found following a micro epididymal sperm extraction (Silber et al., 1994) and testicular biopsy, testicular microdissection was performed or multiple microsurgical testicular biopsies were taken. The mean follow-up of the serum T was 2.4 +/- 1.1 years. RESULTS: Sperm was retrieved in 17/48 (35%) of the men. The per couple take home baby rate if sperm was retrieved was 4/17 (24%). Serum T decreased significantly at follow-up (p < 0.05) and 5/31 (16%) de novo androgen deficiencies developed CONCLUSION: In patients with non-obstructive azoospermia in whom no spermatozoa were found following a micro epididymal sperm aspiration and a simple testicular biopsy, we were able to retrieve spermatozoa in 35% of the men. The take home baby rate was 24% among couples with spermatozoa present upon TESE. De novo androgen deficiency occurred in 16% of the male patients following TESE indicating that, in men with NOA, long term hormonal follow up is recommended after TESE

A stepwise approach to move from a cleavage-stage to a blastocyst-stage transfer policy for all patients in the IVF clinic

STUDY QUESTION: Is a stepwise change management approach an efficacious method to move from a Day 3 transfer policy to a Day 5 transfer policy for all patients in an IVF program? SUMMARY ANSWER: A stepwise change from a Day 3 to a Day 5 transfer policy maintained the live birth rates per oocyte collection cycle (OCC) of the IVF program, with increased single embryo transfer (SET) and reduction of twin pregnancies. WHAT IS KNOWN ALREADY Evidence has shown that the probability of a live birth following IVF with a fresh embryo transfer (ET) is significantly higher after blastocyst-stage transfer than after cleavage-stage transfer. Blastocyst culture and transfer are usually performed in cases of good prognosis patients but many centers keep transferring cleavage-stage embryos for most of their patients because of the higher transfer cancelation rate in a blastocyst transfer policy. STUDY DESIGN, SIZE, DURATION: In January 2012, a Day 5 embryo culture and blastocyst transfer policy including vitrification of supernumerary Day 5 blastocysts were implemented in a stepwise approach. The retrospective descriptive single-center analysis involving a preintervention phase consisted of Day 3 ETs and Day 3 slow freezing from 2010 until 2012. The postintervention phase involved a 6-year period from 2012 until 2017 in which three consecutive changes in the transfer policy were made, each over a 2-year period, based on the number of zygotes on Day 1. The primary outcome was live birth delivery rate per OCC during the stepwise change. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients with at least one zygote available on Day 1 were scheduled for a fresh transfer, either on Day 3 or 5. Cycles with preimplantation genetic testing, freeze-all and oocyte donation cycles and cycles with a Day 2 transfer in the preintervention period were excluded. In the preintervention group, all cycles were scheduled for Day 3 transfer (n=671 OCC) and slow freezing of the remaining Day 3 embryos. In the postintervention period, three periods were analyzed: period 1 (n=1510 OCC; 1-9 zygotes: Day 3 transfer and >9 zygotes: Day 5 transfer); period 2 (n=1456 OCC; 1-4 zygotes: Day 3 transfer and >4 zygotes: Day 5 transfer) and period 3 (n=1764 OCC; Day 5 transfer). All remaining embryos underwent extend culture and were vitrified on Day 5, if developed to at least an early blastocyst. Data were analyzed using a mixed regression model with patient as a random factor. MAIN RESULTS AND THE ROLE OF CHANCE: In the preintervention group, all OCC were scheduled for a Day 3 transfer. In period 1, period 2 and period 3, 20.9%, 61.5% and 100% of the OCCs were scheduled for a Day 5 transfer, respectively. More transfers per OCC were canceled in the postintervention period 2 and period 3 compared to the preintervention period (5.3% and 18.7% versus 3.4%, respectively; P<0.0001). The mean number of embryos used per transfer decreased gradually after the introduction of the Day 5 transfer policy, from 1.620.65 in the preintervention group to 1.120.61 in period 3 (P<0.0001). The percentage of SET cycles increased from 48.4% in the preintervention group to 54.6%, 73.8% and 87.8% in period 1, period 2 and period 3, respectively (P<0.0001). The mean number of cryopreserved surplus embryos was significantly lower in period 3 compared to the preintervention group (1.291.97 versus 1.782.80; P<0.0001). Pregnancy and live birth delivery rate per fresh transfer, respectively, were significantly lower in the preintervention group (26.7% and 19.1%) as compared to period 3 (39.3% and 24.2%) (P<0.0001). Twin pregnancy rate decreased gradually from 11.0% to 8.2%, 5.7% and 2.5% in the preintervention group, period 1, period 2 and period 3, respectively (P<0.0001). Live birth rate and cumulative live birth delivery rates per OCC were significantly higher in group 2 compared to the preintervention period (25.6% and 35.8% versus 18.5% and 25.9%, respectively). Similar live birth and cumulative live birth delivery rates per OCC were achieved between the preintervention period and period 3 (18.5% and 25.6% versus 19.7% and 24.9%; respectively). LIMITATIONS, REASONS FOR CAUTION: The primary limitation is the retrospective design of the study. The allocation of the cycles was done by the number of zygotes available without taking into account both embryological and clinical prognostic factors. Furthermore, the analysis was restricted to cycles where the standard transfer policy was followed. Embryos which were in the morula or compaction stage were not vitrified or cultured to Day 6, which could have contributed to the slight, not statistically significant, drop in live birth rate per OCC in group 3. WIDER IMPLICATIONS OF THE FINDINGS: Live birth and cumulative live birth delivery rate per OCC in an unselected patient population is maintained in a Day 5 transfer policy compared to a Day 3 transfer policy. Additionally, a significantly reduction in twin pregnancy rate and a significant increase in SET were observed in a Day 5 transfer policy. For centers wanting to make the step from Day 3 to Day 5, this study provides a practical stepwise change management approach

No difference in cumulative live birth rates between cleavage versus blastocyst transfer in patients with four or fewer zygotes : results from a retrospective study

STUDY QUESTION Is the cumulative live birth rate (CLBR) per oocyte collection cycle (OCC) comparable after cleavage-stage or blastocyst-stage transfer in combination with supernumerary blastocyst vitrification on Day 5 (D5) in patients with four or fewer zygotes on Day 1? SUMMARY ANSWER The CLBR in a fresh blastocyst-transfer or cleavage-stage transfer policy followed by vitrification on D5 is comparable in patients with four or fewer zygotes. WHAT IS KNOWN ALREADY Blastocyst transfer enhances the self-selection of the embryo and shortens the time to pregnancy in patients with normal or high ovarian response. Whether these advantages are also present in patients with a low ovarian response and/or a limited number of available zygotes is a continuous debate. STUDY DESIGN, SIZE, DURATION This was a retrospective, observational cohort study of 2359 consecutive OCCs between January 2014 and December 2018. According to a shift in transfer policy in our center, 571 OCCs had been scheduled for a fresh transfer on Day 3 (D3) and 1788 on D5. The D5 group was matched to the D3 group by propensity score (PS) matching according to multiple maternal baseline covariates. After PS matching, there were 571 OCCs in each group. PARTICIPANTS/MATERIALS, SETTING, METHODS OCCs scheduled for a D3 transfer (n = 571) or for a D5 transfer (n = 1788) were matched by PS matching in a 1:1 ratio accounting for potential confounding factors associated with CLBR. The model included patient characteristics, such as maternal age and cycle rank, as well as treatment characteristics such as GnRH analog regimen and ovarian response. Embryological variables included the number of zygotes and the number of 6- to 7- and 8-cell embryos on D3. The delivery outcomes of the fresh treatment cycle and the consecutive vitrified-warmed embryo transfers were analyzed up to the first live birth. The primary endpoint of this study was CLBR per OCC. Secondary outcomes were live birth rate per fresh transfer and embryo implantation rate per transferred embryo. MAIN RESULTS AND THE ROLE OF CHANCE The CLBR per OCC was comparable between the D5 and D3 groups (16.8% versus 17.7%, respectively, P = 0.600). Live birth rates per OCC did not differ between a cleavage-stage transfer and blastocyst-stage transfer policy (15.2% versus 12.4%, respectively, P = 0.160). In the D5 group, 201 cycles did not result in a blastocyst to perform an embryo transfer or cryopreservation; in the D3 group, only 59 cycles did not have an embryo transfer because of poor embryo quality (35.2% versus 10.3%, respectively; P < 0.001). A significantly higher number of fresh double embryo transfers were performed in the D3 group compared to D5 (23.8% versus 7.0%, respectively, P < 0.001). LIMITATIONS, REASONS FOR CAUTION Although adjusted for important confounders in the PS matching, BMI and embryo quality of the transferred embryo(s) were not taken into account. This study is limited by its retrospective design and is a single-center study, which may limit the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS The CLBR in a fresh blastocyst-transfer or cleavage-stage transfer policy followed by vitrification on D5 is comparable. A fresh embryo transfer on D3 can still be considered in patients with a poor ovarian response and/or limited number of zygotes when combined with blastocyst vitrification without impacting the overall CLBR of the cycle. STUDY FUNDING/COMPETING INTEREST(S) No external funding was obtained for this study. There are no conflicts of interest to declare