What is the risk factor of hypogonadism after micro TESE in NOA patients? Klinefelter syndrome (KS), past history of cryptorchidism, preoperative testicular volume <8 ml or testosterone <287 ng/dL are significant risk factors of hypogonadism after micro TESE. Micro TESE combined with intracytoplasmic sperm injection (ICSI) is currently standard procedure to treat infertility in cases of NOA. Although many studies have reported the effectiveness of the treatment concerning about sperm retrieval rates (SRR) and the live birth rates, data on safety, especially on the risk of hypogonadism, are limited. Most previous studies, including our past study, regarding the risk of hypogonadism after TESE have been limited to relatively few in number of patients and the investigations only of the changes of mean serum testosterone levels. This study retrospectively investigated 535 NOA patients including 336 cases of unexplained NOA, 91 KS, 16 other chromosomal abnormalities, 31 azoospermia factor (AZF)c deletions, 31 past history of cryptorchidism, and 30 post anticancer chemotherapy, who had undergone micro TESE at our institution from September 2013 to August 2018. All of them had been examined serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels before and at least once in 1-3 months after micro TESE. In this study, hypogonadism was defined as total testosterone <250 ng/dL, which is established by the Japanese Society of Men’s Health as diagnostic criteria for late onset hypogonadism syndrome, and/or starting testosterone replacement therapy (TRT). We assessed risk factors of hypogonadism after micro TESE using indicators such as age, preoperative testicular volume and testosterone levels, past medical history, unilateral or bilateral, first time or not micro TESE. In total of 535 men, FSH and LH after micro TESE significantly increased vs baseline (26.2 vs 29.9 IU/L, 9.6 vs 12.8 IU/L, respectively). On the other hand, testosterone levels significantly decreased after surgery (351.2 vs 297.5 ng/dL). Although postoperative hypogonadism was found in 42% (227/535), many of whom were cases of KS or preoperative testosterone levels <250 ng/dL. Sixteen men with KS, 3 men with unexplained NOA, and 2 men with past history of cryptorchidism started TRT because they complained clinical symptoms after micro TESE. Of the 21 men who started TRT, only 5 had new-onset low testosterone levels after micro TESE. According to the assessment of any association of various indicators and low postoperative total testosterone levels using multiple logistic regression analysis, significant risk factors of hypogonadism early after micro TESE were cases of KS (OR 11.4, 95% CI 4.4-29.9), preoperative testosterone levels <287 ng/dL (OR 7.5, 95% CI 4.7-12.0), preoperative testicular volume <8 ml (OR 3.9, 95% CI 2.3-6.4), past history of cryptorchidism (OR 2.9, 95% CI 1.1-7.8). Most examinations of postoperative hormone levels were performed in short-term period after micro TESE, so we could only assess the risk of postoperative hypogonadism in a short time course in this cohort study. The strength of the current study is that the risk factors of hypogonadism after micro TESE was assessed in a large population of NOA men with various etiologies. The results of this study provide useful clinical information about the risk of postoperative hypogonadism for NOA patients considering micro TESE. not applicable

Abstract Study question Are intravenous immunoglobulins (IVIG) effective for the selected patients who experienced unexplained recurrent pregnancy loss (RPL) that occurred at the same gestational weeks every time? Summary answer IVIG before and after the gestational week-limit (GWL), where miscarriage occurred at the same gestational weeks every time, may improve pregnancy outcomes in RPL patients. What is known already There is no established treatment for patients with unexplained RPL. Some investigators have indicated that IVIG may exhibit therapeutic efficacy in women with unexplained RPL. Since it has been reported that live birth rate significantly increased in women with four or more RPL of unexplained etiology, who received a high dose IVIG at 4-5 weeks of gestation in 2022, ESHRE Guideline Group on RPL (2022) has changed the recommendation to the following: the use of repeated and high doses of IVIG very early in pregnancy may improve live birth rate in women with four or more unexplained RPL. Study design, size, duration We performed a retrospective study between September 2013 to March 2023 in two fertility centers. We included 164 patients in the study who experienced 2 or more miscarriages between 5 and 21 weeks of gestation that occurred at the same gestational weeks every time, who had all negative results for our routine RPL work up and still unsuccessful result after treating these conditions, and whose products of conceptus (POC) revealed at least one normal karyotype. Participants/materials, setting, methods IVIG (Venoglobulin IH 5%, Japan Blood Products Organization, 0.4g/kg) injection was performed twice before and after 1 week of GWL. We divided 164 patients into IVIG group and non-IVIG group by their own choice. The primary outcome was live birth rate, and the secondary outcome was modified live birth rate excluding pregnancies with abnormal fetal karyotype, maternal and neonatal complications. All participants provided written informed consent, and Institutional Review Board approval was obtained. Main results and the role of chance IVIG group (n = 116) and non-IVIG group (n = 48) showed no significant differences in the background of patients on BMI (20.3±3.7 and 21.1±2.8), age (37.4±4.2 and 36.7±3.2) and Childbirth history (20.7% and 23.0%), respectively (average±SD), except for the history of past miscarriages. Average numbers of previous miscarriages on IVIG group and non-IVIG group were 3.2±1.3 and 2.5±0.8 (p < 0.001), respectively. After multivariate analysis for BMI, age, Childbirth history and previous miscarriages, live birth rate of IVIG group (70.7%, 82/116) was significantly higher than that of non-IVIG group (60.4%, 29/48; Odds ratio 3.40, 95% CI: 1.49-7.74, p = 0.003). Similarly, modified live birth rate of IVIG group (73.9%, 82/111) was significantly higher than that of non-IVIG group (63.0%, 29/46; Odds ratio 3.40, 95% CI: 1.49-7.74, p = 0.003). Treatment outcomes when IVIG was used for each number of previous miscarriages, the modified birth rate was 88.3% for two times miscarriages, 77.0% for three times, and 57.1% for four or more miscarriages. Maternal complications were observed in 2 cases in IVIG group (chest tightness, obstetric critical bleeding). There were no significant differences in the birth weight, gestational weeks, preterm birth, or fetal growth restriction of newborns between two groups. Limitations, reasons for caution Since retrospective nature and we did not perform POC tests for all patients whose pregnancies had ended in miscarriage, we could not assert the effectiveness of IVIG. We need to conduct randomized controlled trial using placebo group to demonstrate the IVIG efficacy before and after the GWL using euploid blastocysts. Wider implications of the findings IVIG before and after the GWL adjusted for each patient may improve pregnancy outcomes in RPL patients. Although IVIG is expensive, the current method requires only two IVIG injections, that may be acceptable for much more patients who want to avoid miscarriages and who didn’t use IVIG for economic reasons. Trial registration number NA

Abstract Study question Are intravenous immunoglobulins (IVIG) effective for the selected patients who experienced unexplained recurrent miscarriages (RM) that occurred at the same gestational weeks every time? Summary answer IVIG before and after the gestational week-limit (GWL), where miscarriage occurred at the same gestational weeks every time,may improve pregnancy outcomes in RM patients. What is known already Treatment for patients with unexplained RM are challenging. Since the efficacy of immunotherapy with paternal mononuclear cells has been denied in 1999, some treatment options (e.g., intralipid, G-CSF) have been published with conflicting results. In terms of IVIG, the same story has been described. Because previous studies for IVIG treatment included very heterogeneous group of patients, different dose, different intervals of IVIG, and different starting time of infusions. Recently, a double-blind, randomized, placebo-controlled study for unexplained RM women has been published in 2022, which revealed that IVIG (0.4g/kg) for five consecutive days at 4-5 weeks of gestation improved pregnancy outcomes. Study design, size, duration We performed a retrospective study between September 2013 and May 2021 in two fertility centers. We included 106 patients in the study who experienced 2 or more miscarriages between 5 and 21 weeks of gestation that occurred at the same gestational weeks every time, who had all negative results for our routine RM work up and still unsuccessful result after treating these conditions, and whose products of conceptus (POC) revealed at least one normal karyotype. Participants/materials, setting, methods IVIG (Venoglobulin IH 5%, Japan Blood Products Organization, 0.4g/kg) was injected twice before and after 1 week of GWL. If the GWL was 8 weeks of gestation, IVIG should be injected 7 and 9 weeks. We defined successful IVIG treatment as live birth. When the pregnancy ended in miscarriage, POC was performed as much as possible. All participants provided written informed consent, and Institutional Review Board approval was obtained. Main results and the role of chance Of 106 patients, average age was 37.5 years (28-47 years) and the mean number of previous miscarriages was 3.1. Total 128 cycles of IVIG attempt resulted in 90 (70.3%) successful pregnancies, 36 miscarriages and 2 biochemical pregnancies. After excluding abnormal karyotype of POC (N = 7), 68.6% (83/121) was successful. Per patients, 81.1% (86/106) had at least one live birth. Of 32 patients who experienced miscarriages at the first IVIG attempt, 16 patients got pregnant. Following second IVIG attempt resulted in 12 live births (75.0%). The average weight of live birth babies was 3038g and the birth week was 38.8 weeks of gestation (34-41 wk) for singleton pregnancy (N = 83), whereas 2529g with 35.9 weeks of gestation (33-37 wk) for twin pregnancy (N = 7). Four (4/83, 4.8%) and five (5/7, 71.4%) preterm deliveries were observed for singleton and twin pregnancy, respectively. One baby showed pulmonary hemorrhage resulting in hospitalization in the Neonatal Intensive Care Unit, other live birth babies were without any abnormal findings. Hypertensive disorders of pregnancy were noted in two women resulting in cesarian section delivery. Limitations, reasons for caution This study was retrospective study without any control group and was conducted at only two fertility centers. In future clinical research, it is necessary to conduct randomized controlled trials using placebo group to demonstrate the effectiveness of IVIG before and after the GWL using euploid blastocysts. Wider implications of the findings IVIG before and after the GWL adjusted for each patient may improve pregnancy outcomes in RM patients. Although IVIG is expensive, the current method requires only two IVIG injections, that may be acceptable for much more patients who want to avoid miscarriages and who didn’t use IVIG for economic reasons. Trial registration number not applicable

Abstract Study question What is sperm retrieval rate (SRR) by micro TESE and the clinical outcomes using testicular sperm in couples with the history of cryptorchidism? Summary answer NOA couples with the history of cryptorchidism had a higher SRR by micro TESE but lower clinical outcomes by ICSI compared of unexplained NOA. What is known already Undescended testis (UT) which is exposed to a higher temperature compared with the scrotal temperature is associated with impairment of germ cell maturation, and progressive Leydig and Sertoli cell atrophy, and subsequent infertility in adulthood. There have been very few studies of ICSI with a focus on, or large enough numbers to examine, the specific outcomes associated with male factor infertility, however improvement in sperm retrieval techniques including micro TESE and micromanipulation techniques, such as ICSI, has led to excellent fertilization and pregnancy outcomes of treatment cycles. Study design, size, duration We performed a retrospective study based on two reproduction centers in Japan and evaluated 1521 azoospermic patients in our clinics between September 2013 and December 2022. We investigated SRR by micro TESE in these patients and therefore aimed to evaluate the prevalence and the significance of ICSI outcomes with embryonic development in NOA couples with the history of cryptorchidism. Participants/materials, setting, methods We evaluated SRR of micro TESE, two pronuclei (2PN) oocyte rates, blastocyst development, good-quality blastocyst (Grade 3BB and above on day 5 by the Gardner scoring), and clinical pregnancy rates per embryo transfer (ET) in 72 NOA cases with the history of UT, 953 cases of unexplained NOA, not including after orchidopexy, Klinefelter syndrome, cryptozoospermia, mumps orchitis, and 284 cases of obstructive azoospermia (OA). Statistical analysis was performed using unpaired t-tests and chi-squared tests. Main results and the role of chance SRR of first attempt micro TESE in UT (44/56=78.6%) was higher than unexplained NOA (160/748=21.4%) (p < 0.001). Spermatozoa were successfully retrieved in 13 of 22 (59.1%) UT group and 36 of 226 (15.9%) unexplained NOA who had previously undergone micro TESE with no sperm found. No correlation was found between serum FSH, LH, and T level with the success of sperm retrieval. Testicular volume and patient age at orchidopexy also did not affect the SRR for micro TESE. 2PN oocytes, blastocysts development, and good-quality blastocysts rates were 45.5%, 47.4%, and 18.9% in UT, 51.2%, 45.0%, and 20.9% in unexplained NOA, and 62.6%, 52.1%, and 23.7% in OA, respectively. Clinical pregnancy rates per ET were 29.3% in UT, 32.3% in unexplained NOA, and 41.6% in OA. Significant differences were only observed in 2PN oocytes between unexplained NOA and OA (p < 0.05) and clinical pregnancy between UT and unexplained NOA (p < 0.05), and OA and unexplained NOA (p < 0.01). Several UT patients showed a very small number of spermatozoa and even only immotile sperm of retrieved by micro TESE. Limitations, reasons for caution We included the patients only after a surgery of cryptorchidism, but not a delayed testicular descent without surgery. The cohort size of this study is not small, however, our screened population of azoospermic patients may be biased. Wider implications of the findings This study shows a high impact in micro TESE and ICSI outcomes with embryonic development for the NOA couples with the history of cryptorchidism. Our study emphasizes that history of cryptorchidism provides clinically valuable prognostic information to couples considering surgical sperm retrieval. Trial registration number not applicable

Abstract Study question To evaluate the effectiveness of chlormadinone acetate (CMA) for preventing premature LH surge in patients with normal ovarian reserve compared to cetrorelix. Summary answer In progestin-primed ovarian stimulation (PPOS) than GnRH antagonist (GnRH-ant), the incidence of premature LH surge was significantly lower, without significant difference in oocyte maturation rate. What is known already The GnRH-ant protocol is one of the conventional protocols which has some disadvantages including increased premature LH surge rate and cancelation rate. In recent years, the PPOS protocol has attracted attention as a new ovarian stimulation using progestin as an alternative to GnRH analog for suppressing a premature LH surge, however its efficacy is still controversial. In addition, many studies have investigated the reproductive outcomes of PPOS using medroxy-progesterone acetate or dydrogesterone; however, there are few reports of CMA, an oral progestin, which is inexpensive and widely used in Japan. Study design, size, duration This retrospective cohort study was performed in a reproduction center between March 2018 and October 2020 which included 977 Japanese patients with normal ovarian reserve undergoing PPOS with CMA (n = 299), or GnRH antagonist (GnRH-ant) with cetrorelix (n = 608) in their first IVF cycle at the reproduction center. In subgroup analysis, pregnancy outcomes after frozen embryo transfers (FET) between PPOS (n = 284) and GnRH-ant (n = 579) were also compared. Participants/materials, setting, methods The inclusion criteria were patients aged < 40 years and AMH ≧ 1.1 ng/mL, who underwent autologous oocyte retrieval in their first IVF cycle with freeze-all strategy. The primary outcome was the incidence of premature LH surge, the secondary outcomes was oocyte maturation rate. To reduce the impact of treatment bias and potential confounding factors, we conducted logistic regression models with inverse-probability-of-treatment weighting (IPTW). Main results and the role of chance After IPTW, baseline clinical data were well-balanced between the two groups, including age, AMH, BMI, the duration, type, and cause of infertility, antral follicle count, the history of recurrent spontaneous abortion, and previous IVF attempts. The premature LH surge rate was significantly lower with PPOS (3.1%) compared to GnRH-ant (20.1%) (odds ratio, 0.21; 95% confidence interval, 0.11–0.36). No significant differences were found in total gonadotropin dose (2400IU for PPOS vs 2400IU for GnRH-ant, p = 0.136), the number of oocyte retrieval (n = 15 vs n = 15, p = 0.484), oocyte maturation rate (78.8% vs 77.8%, p = 0.275), fertilization rate (73.0% vs 72.0%, p = 0.412), viable embryo rate per oocyte retrieval (40% vs 40%, p = 0.890), and good quality blastocyst rate (72.0% vs 69.6%, p = 0.092). However, the good quality day-3 embryo rate was significantly lower with PPOS (37.2% vs 49.1%, p < 0.05). There were no differences in the incidence of moderate-to-severe OHSS (0.3% vs 0.7%, p = 0.481). In FET cycles, the pregnancy outcomes, such as implantation rate (43.1 % vs 51.9 %, p = 0.013) and clinical pregnancy rate (46.5% vs 54.7%, p = 0.027) were significantly lower with PPOS, however, no significant differences were found in ongoing pregnancy rate (75.6% vs 80.5%, p = 0.325), and live birth rate (72.4% vs 79.5 %, p = 0.142). Limitations, reasons for caution This was a retrospective cohort study conducted in a single center. The participants in this study were limited to Japanese ethnicity. The results need to be validated across different centers and other ethnicities. Wider implications of the findings This is the first report assessing the reproductive outcomes on PPOS using CMA, widely used in Japan. The PPOS with CMA significantly suppressed the premature LH surge rate compared to GnRH-ant protocol, without decrease in oocyte maturation rate. Trial registration number N/A

Abstract Study question What is the frequency of azoospermia factor (AZF) microdeletions and sperm retrieval rate (SRR) by micro TESE in patients with these deletions? Summary answer AZFc is most frequent of Y chromosome microdeletions and a predictor of micro TESE outcome in Japanese azoospermic men. What is known already After Klinefelter syndrome, Y chromosome microdeletions are the second most frequent genetic cause of male infertility, with a prevalence of 2%-10% in non-obstructive azoospermia (NOA) and three spermatogenesis loci in the Y chromosome long arm (Yq11) have been classified as AZFa, AZFb, and AZFc. The classical correlation of histopathology phenotypes with these three microdeletions comprises of complete absence of germ cells (Sertoli cell-only syndrome) in patients with AZFa microdeletions, maturation arrest of meiosis in patients with AZFb microdeletions, and hypospermatogenesis in patients with AZFc microdeletions, however, individual variation in the extent of deletions has led to various spermatogenic phenotypes. Study design, size, duration We performed a retrospective study based on two reproduction centers in Japan and evaluated 1373 azoospermic patients in our clinics between September 2013 and December 2021. We investigated the frequency of AZF microdeletions and SRR by micro TESE in patients with these microdeletions and therefore aimed to evaluate the correlation between AZF microdeletions and micro TESE results. Participants/materials, setting, methods A total of 1373 azoospermic were enrolled. After the diagnosis of azoospermia, karyotype analysis and detection of Y chromosome microdeletions were performed on peripheral blood lymphocytes of these patients. Y chromosome microdeletions in AZFa, AZFb, and AZFc regions were detected using Promega Y Chromosome AZF Analysis System version 2.0 (Promega Co.). Twenty sequence-tagged sites within the AZF region of Yq11 and the sex-determining region Y gene were targeted for polymerase chain reaction (PCR) amplification. Main results and the role of chance One hundred and fifty-two AZF microdeletions (11.1%) were detected in the azoospermic patients. The most common deleted region was AZFc (60 cases, 4.4%). Among the patients, 17 (1.2%), 1 (0.1%), 42 (3.1%), 13 (1.0%), and 6 (0.5%) had AZFa, AZFa+b, AZFb+c, AZFb, and AZFa+b+c microdeletions, respectively. When the cases were grouped according to causes of infertility that could be detected, no Y chromosome microdeletions were detected in some groups (cases with Klinefelter Syndrome, hypogonadotropic hypogonadism, congenital absence of vas deferens, and 47, XYY karyotype). Fifty-three azoospermic men with AZFc microdeletions underwent micro TESE, and spermatozoa were detected in 88.7% (47/53) of these men. In contrast, we detected spermatozoa in only 20.4% (109/534) of the azoospermic men without AZF microdeletions. The SRR was much higher in patients with AZFc microdeletions than that of patients without AZF deletions. Although three azoospermic men with AZFb+c microdeletions had also undergone micro TESE following patient request, we did not retrieve spermatozoa. Limitations, reasons for caution We excluded post chemotherapy NOA showing 46, XX and AZFa+b+c deletions post bone marrow transplantation from female donor. Additionally, we did not detect AZFc partial deletion including gr/gr deletion. The cohort size of this study is not small, however, our screened population of infertile men may be biased. Wider implications of the findings NOA patients with AZFc microdeletions had a high percentage of successful sperm retrieval by micro TESE. Our study emphasizes that diagnosis of Y chromosome microdeletions is critical for preconception genetic counseling and provides clinically valuable prognostic information to couples considering surgical sperm retrieval. Trial registration number None

Introduction Chromosomal abnormalities are the most common reason for spontaneous abortion. Conventional cytogenetic analysis by G-banded karyotyping is generally performed for chromosomal analysis, but it has a problem with low-resolution, and is needed long term cell culture and enough experience for diagnosis. More recently, next generation sequencing has been introducing and improving for chromosomal analysis as an accurate, high resolution and throughput method. In this study we aimed to compare the consistency between conventional G-banding and NGS-based chromosomal copy number analysis for chorionic villus from spontaneous abortion. In addition, the frequency of each chromosomal aneuploidy was evaluated. Materials and methods From February, 2018, to April, 2018, chromosomal analysis for 7 chorionic villus samples from spontaneous abortions (from 7 to 9 weeks) were carried out both conventional G-banding and NGS (VeriSeq-PGS, Illumia). The frequency of each chromosomal aneuploidy was investigated for 110 cases from February, 2018 to December, 2018. Results NGS was able to analyze all 7 cases, but G-banding was able to detect 6 cases, and one case was cell growth failure. In 6 cases analyzed by G-banding, the results of 5 cases were consistent with the results of NGS, but one case suspected maternal cell contamination. Among 7 cases analyzed by the NGS, 2 cases were normal male karyotype (46, XY) and 5 cases were autosomal trisomy, implying that there were no cases suspected of maternal cell contamination. Among 110 cases, chorionic villus was not observed under microscope from 18 samples, NGS result was obtained from 92 cases. Seventy-one cases were found to have abnormal chromosomes (71/92, 77.2%), and 21 cases were normal karyotype (21/92, 22.8%). Aneuploidy of chromosome 22 (21.8%), chromosome 16 (17.9), chromosome 15 (11.9%), chromosome 21 (10.3%) and Chromosome X (10.3%) were more frequently, consistent with previous report. Conclusions Chromosome analysis using NGS not only obtained comparable results to conventional G-banding, but also is able to analyze more accurately and quickly.

Utilization of testicular (TESE) sperm in cryptozoospermic patients is still controversial. There has been no established treatment strategy available for such patients. Some achieve successful outcome with ejaculated (EJ) sperm while some may require surgical sperm retrieval. In order to propose a treatment strategy we attempted to characterize cryptozoospermic patients with successful results by investigating clinical outcome according to the sperm origin and the number of ICSI attempts. Medical records and laboratory data were retrospectively analyzed. As long as motile sperm were found in EJ samples cryptozoospermic couples underwent ICSI initially with EJ sperm, while some couples with no viable sperm available chose to use TESE sperm from their first attempt. We also included couples that had several previous failed cycles (average 4.2) with EJ sperm and subsequently underwent TESE ICSI (EJ-TESE). The rates of fertilization (FR), blastulation (BR), and live birth (LB) per cycle as well as per couple were assessed. Clinical outcome of 67 cryptozoospermic couples consisted of 38 with EJ, 12 with TESE, and 17 with EJ-TESE was evaluated. Among the three groups EJ-TESE showed lowest FR (61.4% in EJ, 62.8% in TESE, and 45.1% in EJ-TESE, P < 0.01) and BR (45.4%, 43.9% and 24.6%, P < 0.05). LBs per cycle were all comparable, 45.6% in EJ, 28.9% in TESE, and 27.3% in EJ-TESE. Interestingly, LB per couple was 68.4% (26/38) in EJ, statistically similar to 91.7% (11/12) in TESE, and 53.0% (9/17) in EJ-TESE, respectively. More importantly, 88% of successful EJ couples achieved LB in less than 3 embryo transfers (ET). In TESE, 91% of couples obtained LB in 4 ETs, while 88% of LB in EJ-TESE was occurred in 2 ETs. In both EJ and EJ-TESE groups, average maternal age with LB was younger than unsuccessful couples (31.5 years vs 38.1 in EJ, 32.9 vs 38.6 in EJ-TESE, P < 0.01), while in EJ-TESE group only paternal age with LB was significantly younger (34.2 vs 41.4, P < 0.05). Finally, none of the male endocrine parameters and testicular volume was associated with ICSI results. Over 80% of couples obtained live birth in two embryo transfers with EJ sperm. Interestingly, well over 90% of couples initiated with TESE achieved live birth. Thus, as far as viable spermatozoa are available, cryptozoospermic couples may undergo up to two ICSI attempts with EJ sperm when a female partner is young. In cases where no motile sperm are available in ejaculates, surgical sperm retrieval is recommended as the first line treatment option.

To compare the clinical results of simple testicular sperm extraction (ST) and micro dissection testicular sperm extraction (MT) in azoospermic patients [obstructive azoospermia (OA), non-obstructive azoospermia (NOA), Klinefelter's syndrome (KS)]. Retrospective study. The subjects were 476 azoospermic patients from 1997 to 2012: the patients from 1997 to 2005 received ST, and the patients from 2006 to 2012 received ST in OA and MT in NOA/KS. We compared the sperm collection rate and clinical pregnancy rate in two groups (ST versus MT). In 476 cases, sperm collection rates of ST vs. ST+MT were 59.4 % (114/192) vs. 50.0% (142/284): P=0.04. The sperm collection rates of ST vs. MT in KS were 31.3% (5/16) vs. 42.4% (14/33): P=0.40. The pregnancy rates of ST vs. MT in KS were 60.0% (3/5) vs. 64.3% (9/14): P=0.86. The numbers of pregnant cases in ST vs. MT were 3 vs. 7 in fresh sperm, 2 vs. 2 in frozen sperm. The numbers of children were 6 vs. 8, respectively. Sperm collection rate in MT has recently decreased, and there are some cases in which sperm is collected in MT but not ST. A further team approach (gynecologist, urologist, lab technician, nurse, and counselor) to reproductive technology is important; also, improvement of ART technology and education of the patients is necessary.

To evaluate the outcome of infants using relatively new technologies- IVM, TESE, AOA- in Assisted Reproductive Technology (ART). Retrospective study. The subjects were 1538 children who were born after fresh or frozen embryo transfer at Kyono ART Clinic in Japan, from 2000 to 2011. The subjects were divided into 4 groups: Group 1, Conventional intracytoplasmic sperm injection (ICSI); Group 2, TESE; Group 3, IVM; and Group 4, AOA. Among 1538 children {Group 1 (1063 singletons, 278 pairs of twins, 27 sets of triplets), Group 2 (87 singletons, 32 pairs of twins), Group 3 (17 singletons, 6 pairs of twins), and Group 4 (26 singletons, 2 pairs of twins)}, low neonatal birth weight rates, congenital abnormality rates, and premature birth (22-36 weeks) rates were compared. From Groups 1 to 4, premature birth rates, and weights were 18.2%/2002g, 11.8/2177g, 26.1%/2269g, and 10.7%/2540g, respectively. Low neonatal birth weight rates were 27.1%, 19.3%, 30.4%, and 21.4%. Abnormality rates were 3.1%, 3.4%, 8.7%, and 4.0%, respectively. There were no significant differences between ICSI and the other groups. The congenital abnormalities found include inguinal hernia, mild antral septal defect and ventricular septal defect due to low birth weight, and the majority of children have healed naturally. A few cases of hyperdactylia, 18 trisomy, 21 trisomy and patent ductus arteriosus were also found. Moreover, physical growth including weight and height was within the normal range up to 6 years old overall. Advanced technology such as TESE, IVM, and AOA do not have negative effects on child birth and development. However we need to continue long-term follow-up to evaluate more cases.

ObjectiveTo evaluate the pregnancy and neonatal outcome after ovulation induction with aromatase inhibitor letrozole or clomiphene citrate (CC).DesignA retrospective study at Kyono ART Clinic from January 2002 to November 2012.Materials and MethodsThe subjects were 1389 couples with 2461 oocyte pick up cycles, divided into two groups: letrozole in 1113 cycles and CC in 1348 cycles. The couples, all gave written, informed consent. Letrozole, at a dose of 5 mg/day, or CC, at a dose of 100mg/day, was given to patients on days 3-7 of menstrual cycles. Patients were treated with hMG or FSH or a combination of the two each day, starting from day 8. Cetrotide 0.25mg/day was administered when the dominant follicle reached 14 mm in diameter. Ovulation was triggered with urinary hCG. We compared the results of assisted reproductive technology (ART) and neonatal conditions in the two groups.ResultsThere were no significant differences between letrozole and CC in mean age (38.8±4.3 vs. 39.7 ±4.2), FR (67.8% vs. 70.2%), good quality embryo on day 3 (46.2% vs. 44.2%), blastocyst formation rate (39.7% vs.39.6%). The cumulative pregnancy rate was significantly higher in the letrozole group in comparison with the CC group (22.7% vs. 16.8%, P=0.00047). There were no differences in the results of neonatal outcomes between the two groups (letrozole group, 137 singletons and 8 sets of twins; CC group, 72 singletons and 6 sets of twins). In the letrozole group, there were two cases of congenital abnormality: one of 21 trisomy and one of polymelia. In the CC group, there was one case of congenital abnormality: a neonatal death stemming from congenital cardiac disease and congenital clubfoot.ConclusionLetrozole and CC resulted in favorable pregnancy and neonatal outcomes and indicated that children were growing normally. It is shown that the two medicines are safe for mothers and fetuses. However, we need to consider further long-term follow up in the future. ObjectiveTo evaluate the pregnancy and neonatal outcome after ovulation induction with aromatase inhibitor letrozole or clomiphene citrate (CC). To evaluate the pregnancy and neonatal outcome after ovulation induction with aromatase inhibitor letrozole or clomiphene citrate (CC). DesignA retrospective study at Kyono ART Clinic from January 2002 to November 2012. A retrospective study at Kyono ART Clinic from January 2002 to November 2012. Materials and MethodsThe subjects were 1389 couples with 2461 oocyte pick up cycles, divided into two groups: letrozole in 1113 cycles and CC in 1348 cycles. The couples, all gave written, informed consent. Letrozole, at a dose of 5 mg/day, or CC, at a dose of 100mg/day, was given to patients on days 3-7 of menstrual cycles. Patients were treated with hMG or FSH or a combination of the two each day, starting from day 8. Cetrotide 0.25mg/day was administered when the dominant follicle reached 14 mm in diameter. Ovulation was triggered with urinary hCG. We compared the results of assisted reproductive technology (ART) and neonatal conditions in the two groups. The subjects were 1389 couples with 2461 oocyte pick up cycles, divided into two groups: letrozole in 1113 cycles and CC in 1348 cycles. The couples, all gave written, informed consent. Letrozole, at a dose of 5 mg/day, or CC, at a dose of 100mg/day, was given to patients on days 3-7 of menstrual cycles. Patients were treated with hMG or FSH or a combination of the two each day, starting from day 8. Cetrotide 0.25mg/day was administered when the dominant follicle reached 14 mm in diameter. Ovulation was triggered with urinary hCG. We compared the results of assisted reproductive technology (ART) and neonatal conditions in the two groups. ResultsThere were no significant differences between letrozole and CC in mean age (38.8±4.3 vs. 39.7 ±4.2), FR (67.8% vs. 70.2%), good quality embryo on day 3 (46.2% vs. 44.2%), blastocyst formation rate (39.7% vs.39.6%). The cumulative pregnancy rate was significantly higher in the letrozole group in comparison with the CC group (22.7% vs. 16.8%, P=0.00047). There were no differences in the results of neonatal outcomes between the two groups (letrozole group, 137 singletons and 8 sets of twins; CC group, 72 singletons and 6 sets of twins). In the letrozole group, there were two cases of congenital abnormality: one of 21 trisomy and one of polymelia. In the CC group, there was one case of congenital abnormality: a neonatal death stemming from congenital cardiac disease and congenital clubfoot. There were no significant differences between letrozole and CC in mean age (38.8±4.3 vs. 39.7 ±4.2), FR (67.8% vs. 70.2%), good quality embryo on day 3 (46.2% vs. 44.2%), blastocyst formation rate (39.7% vs.39.6%). The cumulative pregnancy rate was significantly higher in the letrozole group in comparison with the CC group (22.7% vs. 16.8%, P=0.00047). There were no differences in the results of neonatal outcomes between the two groups (letrozole group, 137 singletons and 8 sets of twins; CC group, 72 singletons and 6 sets of twins). In the letrozole group, there were two cases of congenital abnormality: one of 21 trisomy and one of polymelia. In the CC group, there was one case of congenital abnormality: a neonatal death stemming from congenital cardiac disease and congenital clubfoot. ConclusionLetrozole and CC resulted in favorable pregnancy and neonatal outcomes and indicated that children were growing normally. It is shown that the two medicines are safe for mothers and fetuses. However, we need to consider further long-term follow up in the future. Letrozole and CC resulted in favorable pregnancy and neonatal outcomes and indicated that children were growing normally. It is shown that the two medicines are safe for mothers and fetuses. However, we need to consider further long-term follow up in the future.