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Inflammatory bowel disease (IBD) affects patients in their peak reproductive years. Active IBD increases the risk of adverse pregnancyoutcomes, including miscarriage, intrauterine growth restriction and preterm birth. Most women with IBD will require medication to controltheir disease, both before conception and during pregnancy and breastfeeding. Preconception counselling has been shown to improve pregnancy outcomes. Most IBD medications are considered safe during pregnancy and breastfeeding. A multidisciplinary approach, with the involvementof general practitioners, midwives, obstetric physicians, and obstetriciansand gastroenterologists, is recommended. Three to six months beforeconception, women should be reviewed by their gastroenterologist forpreconception counselling to confirm disease remission, receive education about pregnancy and IBD and have a pregnancy treatment planestablished. Medical treatment should be optimised, with the aim ofachieving sustained remission for at least three to six months beforeconception. Cessation or modification of IBD treatment is usually notnecessary, with the exception of methotrexate, thalidomide and allopurinol, and any changes to medical therapy should be made in consultationwith the treating gastroenterologist. Data on biologic use in pregnancy(TNFi, vedolizumab, ustekinumab) and Tofacitinib will be discussed. Fearof infertility is common among patients with IBD, but women with quiescent IBD generally have normal fertility. Women with Crohn's disease may have reduced fertility if they have active disease or have had anileo-anal pouch. There is no evidence that ulcerative colitis affects fertility. IBD does not affect fertility in men, but some medications, includingsulfasalazine and methotrexate, may cause reduced sperm count and mayneed to be replaced with alternatives pre-pregnancy. Women should bereviewed once per trimester and more regularly if they have active disease. Inadequate gestational weight gain is a marker f

With approximately 131 million new genital tract infections occurring each year, Chlamydia is the most common sexually transmitted bacterial pathogen worldwide. Male and female infections occur at similar rates and both cause serious pathological sequelae. Despite this, the impact of chlamydial infection on male fertility has long been debated, and the effects of paternal chlamydial infection on offspring development are unknown. Using a male mouse chronic infection model, we show that chlamydial infection persists in the testes, adversely affecting the testicular environment. Infection increased leukocyte infiltration, disrupted the blood:testis barrier and reduced spermiogenic cell numbers and seminiferous tubule volume. Sperm from infected mice had decreased motility, increased abnormal morphology, decreased zona-binding capacity, and increased DNA damage. Serum anti-sperm antibodies were also increased. When both acutely and chronically infected male mice were bred with healthy female mice, 16.7% of pups displayed developmental abnormalities. Female offspring of chronically infected sires had smaller reproductive tracts than offspring of noninfected sires. The male pups of infected sires displayed delayed testicular development, with abnormalities in sperm vitality, motility, and sperm-oocyte binding evident at sexual maturity. These data suggest that chronic testicular Chlamydia infection can contribute to male infertility, which may have an intergenerational impact on sperm quality.Copyright © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction.

STUDY QUESTION: Over a time period of 3 years, which order of expectant management (EM), IUI with ovarian stimulation (IUI-OS) and IVF is the most cost-effective for couples with unexplained subfertility with the female age below 38 years? SUMMARY ANSWER: If a live birth is considered worth e32 000 or less, 2 years of EM followed by IVF was the most cost-effective, whereas above e32 000 this was 1 year of EM, 1 year of IUI-OS and then 1 year of IVF. WHAT IS KNOWN ALREADY: IUI-OS and IVF are commonly used fertility treatments for unexplained subfertility although many couples can conceive naturally, as no identifiable barrier to conception could be found by definition. Few countries have guidelines on when to proceed with medically assisted reproduction (MAR), mostly based on the expected probability of live birth after treatment, but there is a lack of evidence to support the strategies proposed by these guidelines. The increased uptake of IUI-OS and IVF over the past decades and costs related to reimbursement of these treatments are pressing concerns to health service providers. For MAR to remain affordable, sustainable and a responsible use of public funds, guidance is needed on the cost-effectiveness of treatment strategies for unexplained subfertility, including EM. STUDY DESIGN, SIZE, DURATION: We developed a decision analytic Markov model that follows couples with unexplained subfertility of which the woman is under 38 years of age for a time period of 3 years from completion of the fertility workup onwards. We divided the time axis of 3 years into three separate periods, each comprising 1 year. The model was based on contemporary evidence, most notably the dynamic prediction model for natural conception, which was combined with MAR treatment effects from a network meta-analysis on randomized controlled trials. We changed the order of options for managing unexplained subfertility for the 1 year periods to yield five different treatment policies in total: IVF-E

Objective: To study the effectiveness of different ovulation induction protocols in infertile women with polycystic ovary syndrome (PCOS) undergoing intrauterine insemination (IUI). Design(s): Retrospective cohort study. Patient(s): Infertile women with PCOS undergoing IUI had ovulation induced with clomiphene citrate (CC), letrozole, or gonadotropins. Main Outcome Measure(s): Live birth and multiple pregnancy rates. Result(s): We performed 1068 IUI cycles in 765 couples. Live birth rates were comparable in CC-stimulated cycles (13.9%), letrozole-stimulated cycles (13.5%, OR 0.96 [95% CI, 0.63, 1.47]), and gonadotropins-stimulated cycles (13.2%, OR 0.94[95% CI, 0.62, 1.43]). Multiple pregnancy rates were 8.3%, 4.1% (OR 0.47 [95% CI, 0.09, 2.42]), and 3.3% (OR 0.34 [95% CI, 0.07, 1.95]) in CC, letrozole and gonadotropins stimulated cycles, respectively. Compared to CC, letrozole generated more often mono-follicular growth (75.9% versus 67.0%; OR 1.55 [95% CI, 1.11, 2.15]) but not more often after gonadotropins (72.9%, OR 1.17 [95% CI, 0.82, 1.66]. Cycles with multi-follicular growth did not result in statistically higher live birth rates than cycles with mono-follicular growth (15.8% vs. 12.7%, OR 1.29 [95% CI 0.89, 1.89]), but more often in multiple pregnancies (15.5% versus 0.8%, OR 22.4 [95% CI, 2.8, 181.6]). Conclusion(s): In women with PCOS undergoing stimulated IUI, CC, letrozole and gonadotropins were equally effective and safe. Since multi-follicular growth increased the multiple pregnancy rates without increasing the overall live birth rate, ovulation induction would strictly aim for mono-follicular growth. Since letrozole had the highest mono-follicular growth rate, we recommend this drug as the treatment of first choice in infertile women undergoing ovulation induction and IUI.Copyright © 2018

Study question: Should couples with low post-wash total motile count (TMC) in the first intrauterine insemination (IUI) cycle continue IUI treatment? Summary answer: Couples with low post-wash TMC in the first IUI cycles can continue IUI treatment without compromising their fertility outcomes. What is known already: IUI is the treatment of first choice for couples with unexplained or mild male infertility. The post-wash TMC in the first IUI cycle can be used to predict pregnancy, and at present many couples switch to IVF after a first poor post-wash semen analysis. However, it is unknown if a poor post-wash TMC in the first IUI cycle is predictive for future IUI outcomes. To study the association between post-wash TMC and outcomes of future IUI cycles, we compared live birth rates in women undergoing IUI in relation to their post-wash semen analysis. Study design, size, duration: We performed a retrospective cohort study in the Reproductive Medicine Centre of Peking University Third Hospital. Participants/materials, setting, methods: We included couples with unexplained or mild male infertility treated with IUI in two consecutive cycles with similar protocols. Women with polycystic ovary syndrome were not included. We compared live birth rates in the second cycle according to different groups in post-wash TMC in the first cycle.We also compared the baseline characteristics and clinical pregnancy between groups with different post-wash TMC. ANOVA and Chi square analysis were conducted in SPSS 19.0. Main results and the role of chance: We studied 4,496 IUI cycles in 2,248 couples, of which 2,732 were unstimulated cycles and 1,764 were cycles stimulated with CC, letrozole or gonadotropins. We sorted data according to their post-wash TMC in the first cycle in ascending order and then divided all patients, into eight equal groups. Medians of sperm count were 0.6, 1.3, 2, 3, 4, 5, 7, and 13. Live birth rates in the second cycle were 6.1%, 6.4%, 7.5%, 8.9%, 6.1%, 7.8%, 6.1

Context: The development of a safe and effective reversible method of male contraception is still an unmet need. Objective(s): Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone. Design(s): Prospective multicentre study. Setting(s): Ten study centers. Participant(s): Healthy men, aged 18-45 years, and their 18- to 38-year-old female partners, both without known fertility problems. Intervention(s): Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks. Main Outcomes Measures: Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate. Result(s): Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8- 97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method). During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59-4.14). The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recoverywas94.8 per 100 continuing users(95%CI, 91.5-97.1).Themostcommonadverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early. Conclusion(s): The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high.Copyright © 2016 by the Endocrine Society.

STUDY QUESTION What are the effects on fertility of cigarette smoke-induced toxicity on male offspring exposed during the gestational/weaning period? SUMMARY ANSWER Maternal cigarette smoke exposure during the gestational/weaning period causes long-term defects in male offspring fertility. WHAT IS KNOWN ALREADY Cigarette smoke is a well-known reproductive toxicant which is particularly harmful to both fetal and neonatal germ cells. However, recent studies suggest a significant portion of young mothers in the developed world still smoke during pregnancy. In the context of male reproductive health, our understanding of the effects of in utero exposure on offspring fertility is limited. STUDY DESIGN, SIZE, DURATION In this study, 27 C57BL/6 5-week-old female mice were exposed via the nose-only to cigarette smoke (treatment) or 27 were exposed to room air (control) for 6 weeks before being housed with stud males to produce litters. In the treatment group, smoke exposure continued throughout mating, pregnancy and lactation until weaning of pups at 21 days post birth. Male offspring were examined at post-natal days 3, 6, 12, 21 and 98 (adult). PARTICIPANTS/MATERIALS, SETTING, METHODS Approximately 108 maternal smoke-exposed C57BL/6 offspring and controls were examined. Spermatogenesis was examined using testicular histology and apoptosis/DNA damage was assessed using caspase immunohistochemistry and TUNEL. Sertoli cell morphology and fluctuations in the spermatogonial stem cell population were also examined using immunohistochemistry. Microarray and QPCR analysis were performed on adult testes to examine specific long-term transcriptomic alteration as a consequence of maternal smoke exposure. Sperm counts and motility, zona/oolemma binding assays, COMET analysis and mitochondrial genomic sequencing were also performed on spermatozoa obtained from adult treated and control mice. Fertility trials using exposed adult male offspring were also performed. MAIN RESULTS AND THE R

Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT). For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line.Copyright © 2015 Liu et al.

Study question: To prospectively study early life influences, in-utero, childhood and adolescence, that may impact on markers of testicular function: testicular volume (TV), sperm production (total motile sperm [TMS], sperm chromatin structural assay [SCSA], and hormone production (serum FSH, LH, testosterone [T], and inhibin B [InhB]), in men aged 20-22 years. Summary answer: 26.3% of men had an initial semen sample with abnormal morphology 18.9% had low total sperm number according to the WHO minimal criteria; there was a significant correlation between the total motile sperm count and testicular volume. In-utero growth restraint and maternal smoking were associated with reduced TMS in adulthood. What is known already: It is alleged that sperm counts are decreasing, with evidence for adverse effects of chronic smoking and in-utero exposure, although there is conflicting evidence for the effect of intrauterine growth restraint upon sperm production. Adult adiposity is associated with adverse effects on sperm counts, SCSA and hormonal markers of testicular function. Such studies are prone to selection bias as the cohorts have very low recruitment rates and compromise individuals with biased fertility status. Study design, size, duration: Prospective cohort study, using theWestern Australian Pregnancy (Raine) Cohort, who underwent regular assessment since birth in 1990-1991, including fetal measurements for half the cohort. Part of the 20 year follow-up involved testicular assessment. Of available 911 men; 696 attended general assessment and 423 took part in the testicular study. Participants/materials, setting, methods: 404 men underwent testicular ultrasound examination 365 underwent >=1 semen assessments (recruitment was 40% overall 46.1% of available cohort 60.3% of attendees of the 20 year assessments). General health assessment and DEXA scanning for adiposity was performed at a teaching hospital, and ultrasound examination and semen assessments at separate loca

Background: Insufficient vas length for performing a tension-free vasovasostomy is a problem occasionally encountered by microsurgeons. Herein we evaluated utilization of a non-vascularized vas deferens autograft in a rat model. Methods. Segments of isolated vas deferens, 2.5 cm in length, were used as bilateral autografts in 15 rats. Each autograft was implanted between the two transected ends of vas deferens using end-to-end anastomosis. Fertility, sperm motility, and graft survival was evaluated and compared with the control group. Result(s): At the end of the 3 months, 9/15 (60%) rats were able to breed successfully and 24 (80%) vas grafts were patent and viable. Large granulomata developed at the proximal anastomosis sites in 6 (20%) autografts that failed. Unilateral minimal fluid leakage was observed in 6 (20%) of the proximal (testicular end) anastomosis sites in those rats that were able to breed. Histological evaluations demonstrated that graft survival was associated with mild to severe changes in the structure of the vas autograft. On semen analysis 76% of the sperms in the experimental group had forward motility compared to 78% in the control group (p > 0.05). Conclusion(s): Vas autograft can successfully be performed in a rat model with ultimate breeding capability.Copyright © 2014 Kadioglu et al.; licensee BioMed Central Ltd.

Objective To define RABL2A localization in human sperm and to assess any potential association between RABL2A variants and male infertility associated with oligoasthenospermia. Design Genetic association study. Setting Public university. Patient(s) Australian men: 110 oligoasthenospermic infertile and 105 proven fertile. Intervention(s) Human semen samples processed by immunostaining with high-throughput-sequencing platform to screen the entire protein-coding and flanking exon/intron regions of the RABL2A gene. Main Outcome Measure(s) Presence of RABL2A in human sperm and frequencies of RABL2A genetic variants in fertile and infertile men. Result(s) RABL2A localization in sperm was highly conserved between mouse and human, being localized to the tail. Direct DNA sequencing revealed 23 RABL2A genetic variants, including 16 intronic, 6 untranslated region (UTR), and one exonic missense variants. Of these, eight variants have not been previously reported. Although the majority of these variants showed no significant association with fertility status, allelic frequency of the intronic variant 114391996 delC was significantly increased in oligoasthenospermic men. Bioinformatics analysis suggested that the 114391996 delC allele would alter the splicing of RABL2A pre-mRNA. Conclusion(s) Our data suggest the 114391996 delC allele in the RABL2A gene may act as a risk factor for oligoasthenospermic infertility in Australian men. © 2014 by American Society for Reproductive Medicine.

Background. Androgens acting via the androgen receptor bring about stimulation and maintenance of spermatogenesis. If mutations in the androgen-receptor gene interfere with the receptor's function, this effect may partly account for impaired spermatogenesis. We aimed to find out whether expansion of a trinucleotide repeat in the androgen-receptor gene is associated with male infertility. Methods. We analysed 67 coded semen and blood samples from a predominantly white group of male infertility patients and controls. Clinical analyses included cause of infertility, sperm count, and reproductive hormone concentrations. Analysis of trinucleotide (CAG) repeat length and point mutations in the androgen-receptor gene was done by PCR, single-stranded conformational polymorphism,and DNA sequencing. Findings. Screening and characterisation of the androgen-receptor gene in 35 patients and 32 controls showed no point mutations in the gene. 30 of the infertile patients had idiopathic azoospermia or oligozoospermia, and these men had significantly longer CAG repeat tracts than controls (mean 23.2 [SE 0.7] vs 20.5 [0.3], p = 0.0001). The odds of having CAG repeat lengths of 20 were six-fold higher for fertile men than for men with a spermatogenic disorder. Interpretation. Our results indicate a relation between CAG repeat length in the androgen-receptor gene and the risk of defective spermatogenesis. With the use of intracytoplasmic sperm injection, this mutation could be inherited, possibly leading to an increase in male infertility in future generations. Should further elongation of the CAG repeat occur in these future generations, there is an added risk of increased severity of male infertility, and potentially an increased incidence of neurodegenerative disease.

Testosterone (T) treatment suppresses gonadotropin levels and sperm counts in normal men, but the addition of a progestin may improve the efficacy of hormonal contraception. This study aimed to investigate the speed and extent of suppression of testicular germ cell number induced by T plus or minus progestin treatment and correlate these changes with serum gonadotropins and inhibin B levels, testicular androgens, and sperm output. Thirty normal fertile men (31-46 yr) received either testosterone enanthate (TE, 200 mg im weekly) alone or TE plus depot medroxyprogesterone acetate (DMPA, 300 mg im once) for 2, 6, or 12 wk (n = 5 per group) before vasectomy and testis biopsy. Five men (controls) proceeded directly to surgery. The inclusion of DMPA led to a more rapid fall in serum FSH/LH levels (time to 10% baseline: FSH; 12.6 +/- 2.6 vs. 7.9 +/- 1.4 d; LH, 9.9 +/- 3.4 vs. 3.4 +/- 1.7 d, TE vs. TE+DMPA, respectively, mean +/- SD, both P < 0.0001), yet the mean time to reach a sperm count 10% of baseline was not different (23.7 +/- 7.3 vs. 25.3 +/- 13.9 d, NS). The maximum extent of FSH/LH suppression was identical at 12 wk (mean serum FSH 1.2 and 1.6%, and mean LH 0.3 and 0.2% of baseline: TE vs. TE+ DMPA, respectively) as was sperm count suppression (5 of 5 and 4 of 5 men, respectively, with sperm counts <=0.1 x 106/ml). Serum inhibin decreased to 55% control at 12 wk in the TE+DMPA group (P < 0.05) but was unchanged by TE treatment (86% control, NS). Testicular T levels declined to approximately 2% of control levels, but testicular dihydrotestosterone and 5alpha-androstane-3alpha, 17beta-diol (Adiol) levels were not different to control. Germ cell numbers as determined by stereological methods did not differ between TE and TE+DMPA except at 2 wk when type B spermatogonia and early spermatocytes were significantly lower in the TE+DMPA group (P < 0.05). In all groups, a marked inhibition of Apale->B spermatogonial maturation was seen along with a striking inhibition of

Semen quality is said to have been declining over the past 50 years. The biological significance of these changes is emphasized by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and cryptorchidism. The increase in regional frequency of testicular abnormalities over a relatively short period of time may be due to local environmental factors, including the comparatively recent fashion for wearing tight-fitting underwear. Data also indicates that prenatal exposure to environmental agents can affect the development of the male genital tract. From the reproductive point of view, an increased environmental impact on the human male gonad is of concern and merits the development of sensitive techniques that can detect deleterious agents.

BACKGROUND AND OBJECTIVES: Current immunoassays for detecting serum FSH and LH are not sufficiently sensitive to detect the markedly reduced levels in men undergoing steroidal hormonal treatment for contraceptive purposes. The purpose of this study was to increase the sensitivity of available LH and FSH immunofluorometric (Delfia) assays in order to allow a better understanding of the importance of gonadotrophin suppression in achieving the optimal suppression of sperm count. DESIGN AND PATIENTS: Assay conditions were modified by increasing serum sample volume, the inclusion of either FSH- or LH-depleted serum to reduce the resulting matrix effects and extending incubation times. The microassays were applied to serum from 10 men administered testosterone enanthate with or without depot medroxyprogesterone acetate for 12 weeks as part of a contraceptive trial. RESULT(S): The assay sensitivities were increased to 0.005 IU/l for LH and 0.010 IU/l for FSH, representing a five- to six-fold increase in sensitivity compared with existing assays. In the clinical trial, serum LH levels were suppressed to near or below the level of assay detection (mean 0.014 IU/l, <0.4% of pretreatment values) while in eight of 10 men, plasma FSH levels were detectable (0.04-0.07 IU/l, 1-5% of pretreatment values). These FSH levels would not have been detected by current assays. CONCLUSION(S): The increased sensitivities of the LH and FSH assays enabled the detection of gonadotrophins that were <0.4% of pretreatment serum levels. Using these methods, serum LH was suppressed to nondetectable or near nondetectable levels while serum FSH was highly suppressed but still detectable in the majority of men undergoing steroidal treatment for contraceptive purposes.

There are few published data on the recovery of fertility after 'little' Bu-Cy (busulfan 16 mg/kg, cyclophosphamide 120 mg/kg) conditioning for BMT. To address this, we identified 19 females aged less than 40 years at transplant and 47 males from a single centre who were alive a minimum of 2 years after BMT with little Bu-Cy as conditioning and who were evaluable for testing. FSH, LH, testosterone and inhibin B levels were measured in males. Twenty-six also had semen analysis, a median of 5 years post transplant; 21 had detectable sperm, with 11 having counts >20 x 106/ml. There was an association between prolonged chronic graft-versus-host disease and low sperm counts. FSH and inhibin B levels correlated with sperm counts but not to the extent that they could reliably predict counts in individual patients. An additional six of seven males attempting to father children did so, a median of 3.2 years post transplant. Low testosterone levels were noted in 12% of males, most of whom had symptoms consistent with androgen deficiency. FSH, LH and oestradiol levels in the absence of hormone replacement therapy were measured in females; all remained amenorrheic with endocrine evidence of ovarian failure. These results have implications for fertility counselling and hormone replacement therapy both pre-and post BMT.

Context: Management of male infertility and/or androgen deficiency requires accurate hormonal measurements with valid reference intervals. Objective(s): The objective of this study was to develop a valid reference panel of blood samples from healthy eugonadal young men with verified normal reproductive function and to use this panel to evaluate the performance of seven fully automated, commercial multiplex immunoassay platforms used to measure serum total testosterone (T), LH, and FSH. Design(s): This was an observational study of consistency among seven different automated immunoassays for each of total T, LH, and FSH. Each method was implemented in two laboratories, with each repeating the analysis of the full reference panel samples twice. Serum T concentrations were also measured by gas chromatography/mass spectrometry (GC/MS), and serum inhibin B levels were determined by an ELISA. Setting(s): The study was performed at commercial, high-volume, clinical pathology laboratories. Participant(s): From 147 men screened, sera from 124 healthy, reproductively normal men (age, 21-35 yr) with normal sperm output were used as a reference panel. All laboratories selected for elite performance in the national immunoassay quality assurance program agreed to participate. Main Outcome Measure(s): For each of the 868 assays, descriptive statistics were calculated in the natural and log-transformed scales and were analyzed by nested, repeated measures ANOVA after log transformation. Reference intervals, defined as 95% confidence limits, were calculated using arithmetic (natural scale), geometric (log scale) and nonparametric methods. Result(s): Descriptive statistics and reference intervals for serum T, LH, and FSH differed widely and significantly between methods, but variation between laboratories for the same assay was negligible. All T methods showed significant differences in regression slope and intercept in deviance plots as well as in estimated reference ranges compared

Background. Infertility is both a clinical and a public problem, affecting the life of the couple, the healthcare services, and social environment. Standard semen analysis is the surrogate measure of male fertility in clinical practice. Objective. To provide information about the relationship between semen parameters and spontaneous conception. Methods. We evaluated retrospectively 453 pregnancies that occurred among 2935 infertile couples evaluated at an infertility clinic of a tertiary-care university hospital, between 2004 and 2009. Results. Normal semen analysis was present only in 158 patients; 295 subfertile patients showed alterations in at least one seminal parameter. A reduction in all seminal parameters was observed in 41 patients. Etiological causes of male infertility were identified in 314 patients. Conclusion. Our data highlights the possibility of a spontaneous conception with semen parameters below WHO reference values. Therefore, we support the importance of defining reference values on a population of fertile men. Finally, we analyzed the related ethical issues. Copyright © 2012 D. Milardi et al.

Variance components of sperm production traits (volume in ml, V; concentration in ×10 6 sperm/ml, CN; sperm production in ×10 6 sperm, PROD) were estimated in a paternal line of rabbit selected for 25 generations based on daily weight gain (DG, g/day) between 28 and 63 days of age. Features of the marginal posterior distributions for ratios of genetic variance, variance owing to non-additive plus environmental permanent male effects and variance owing to common litter of birth effects with respect to phenotypic variance are reported. The correlations between sperm production traits and the selection criteria were also estimated. Three sets of two-trait analyses were performed, involving 12908 records of DG, 2329 ejaculates corresponding to 412 bucks and 14700 animals in pedigree file. The heritabilities (h 2) of the semen traits were 0.13 ± 0.05, 0.08 ± 0.04 and 0.07 ± 0.03 for V, CN and PROD, respectively. The permanent environmental effects were lower than the corresponding values of h 2 and varied between 0.06 and 0.11. A favourable and moderate genetic correlation was observed between V and DG (0.36 ± 0.34; p > 0: 0.83), together with a non-favourable and moderate correlation between permanent environmental effects owing to common litter of birth for both traits (-0.35 ± 0.35; p < 0: 0.85). On the other hand, the correlation between male permanent environmental effects for semen traits and DG was moderate and non-favourable (-0.51 ± 0.29 with p < 0: 0.95 for DG-CN, and -0.31 ± 0.37 with p < 0: 0.79 for DG-PROD). © 2010 Blackwell Verlag GmbH.

Background: Quantification of changes in semen may give insight into the testosterone (T)-induced disruption of spermatogenesis in man. Method(s): A model analogous to flushing of sperm from the genital tract after vasectomy was used to quantify the time course of semen changes in subjects participating in male contraceptive trials using 800 mg T-implant (n = 25) or 200 mg weekly intramuscular injection (IM-T; n = 33). A modified exponential decay model allowed for delayed onset and incomplete disruption to spermatogenesis. Semen variables measured weekly during a 91-day period after initial treatment were fitted to the model. Result(s) and Conclusion(s): Sperm concentration, total count, motility and morphometry exhibited similar average decay rates (5 day half-life). The mean delay to onset of decline in concentration was 15 (IM-T) and 18 (T-implant) days. The significantly longer (P < 0.005) delays deduced for the commencement of fall in normal morphology (41 days), normal morphometry (40 days) and sperm viability (43 and 55 days), and the change of morphometry to smaller more compact sperm heads are consistent with sperm being progressively cleared from the genital tract rather than continued shedding of immature or abnormal sperm by the seminiferous epithelium. A significant negative relationship was found between lag time and baseline sperm concentration, consistent with longer sperm-epididymal transit times associated with lower daily production rates. © The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Background: Testicular regulation of inhibin B may be influenced by the germ cell complement. Method(s): We examined the effects of gonadotrophin stimulation on serum inhibin B and pro-alphaC in 25 normal men at (i) control (stimulation test 1), (ii) after spermatogenic suppression induced by testosterone plus progestin treatment (stimulation test 2), and (iii) during spermatogenic recovery induced by FSH and/or hCG treatment (stimulation test 3). For each test, subjects received a single injection of 1200 IU FSH or 5000 IU hCG or both. Result(s): Inhibin B and pro-alphaC fell with spermatogenic suppression (75 and 51% of pre-treatment baseline respectively, P < 0.05). Inhibin B response to FSH (130-144%) was similar in controls and after germ cell suppression. Pro-alphaC response after germ cell suppression compared with control was significantly increased (P < 0.05) with both FSH (210-229% versus 140-185%) and hCG (254-261% versus 145%). All treatments partially restored spermatogenesis with no clear relationship apparent between inhibin B and sperm count. Conclusion(s): We conclude that: (i) serum inhibin B and pro-alphaC are only partially gonadotrophin dependent, (ii) spermatogenic suppression does not modify inhibin B response to FSH but enhances pro-alphaC response to both FSH and hCG, and (iii) inhibin B is a poor marker of spermatogenesis in this model of gonadotrophic manipulation in normal men.

Objective: To determine the validity of the criteria currently used to select fertile sperm donors. Design(s): Retrospective study of the outcome of donor insemination treatment cycles over a 15-year period. Setting(s): The Reproductive Medicine Clinic of Prince Henry's Institute of Medical Research (formerly Medical Research Centre, Prince Henry's Hospital, South Melbourne, Victoria, Australia). Patient(s): Couples (1,299) presented with severe male factor infertility (azoospermia or severe oligozoospermia) and were treated by donor insemination (10,796 treatment cycles) using cryopreserved semen from 292 normal healthy men aged between 18 and 46 years as sperm donors. Main Outcome Measure(s): Semen characteristics, including volume, count, motility, motility index, normal morphology, live cells, and post-thaw motility, were analyzed by logistic regression analysis to determine which groups of factors were related independently and significantly to pregnancy rates. Result(s): The pregnancy rate for donor insemination was 8.9% per cycle. By logistic regression count, normal morphology, post-thaw motility (%), and post-thaw motility index together explained 28% of the variance of the pregnancy rates. Other factors, including prethaw motility characteristics (percent motility and motility index), donor age, weight, LH, FSH, and T levels, were not significant. Conclusion(s): The standard parameters of sperm count, morphology, and post-thaw motility are the most important factors for the selection of highly fertile donors. As most of the variability in the pregnancy rates resulted from other undetermined factors related both to the donor and the recipient, it is suggested that the pragmatic approach of discarding donors after a reasonable number of treatment failures (20 to 50) should continue.

The proportion of spermatozoa exhibiting the vigorous motility behaviour termed 'hyperactivation' (HA) has been shown to be increased following removal of seminal plasma and stimulation with chemical agents such as pentoxifylline. The aim of this study was to examine the relationship between the proportion of HA in cryopreserved semen samples from sperm donors and the corresponding pregnancy rates achieved by donor insemination. Cryopreserved samples from 20 men were incubated in the presence or absence of 3 mM pentoxifylline for 1 h and the %HA determined in each sample. The relationship between pregnancy rate, the proportion of HA spermatozoa in control and pentoxifylline-treated groups and the change in %HA following pentoxifylline treatment (DELTAHA) as well as the mean semen characteristics for each donor [sperm count, motility (%), motility index, normal morphology (%), post-thaw motility (%) and post-thaw motility index] were examined by logistic regression of the occurrence of clinical pregnancy with each insemination. Both DELTAHA and mean post-thaw motility index were significantly related to pregnancy rates and together accounted for 64% of the observed variation in pregnancy rates.