James D.M. Nicopoullos

Sperm DNA fragmentation in subfertile men: the effect on the outcome of intracytoplasmic sperm injection and correlation with sperm variables.

To present the first UK data on sperm DNA fragmentation levels in subfertile men and fertile controls, the correlation with semen variables, and to assess the effect on the outcome of intracytoplasmic sperm injection (ICSI).

A decade of sperm washing: clinical correlates of successful insemination outcome

BACKGROUND Since 1999, we have treated HIV-positive men with sperm washing as part of a risk-reduction programme. METHODS Retrospective analysis of the sperm-washing database from the treatment of 245 couples with 439 cycles of intrauterine insemination assessed the effects of patient factors (age, maternal FSH, rank of attempt), markers of HIV-disease [time since diagnosis, CD4 count, viral load (VL), use of highly active antiretroviral therapy (HAART)], cycle factors (natural versus stimulated, number of follicles, fresh versus frozen sperm) and sperm parameters on clinical (CPR) and ongoing pregnancy rate (OPR). RESULTS Overall 111-245 (45.4%) couples achieved a clinical pregnancy (CPR: 13.5% and OPR: 9.6% per insemination) with no seroconversions. The mean duration since HIV diagnosis was 5.8 years, 73% of men were on antiretroviral therapy, there was an undetectable VL in 64% and the median CD4 was 409 cells/mm(3). A significantly decreased OPR and a non-significantly increased miscarriage rate (MR) was observed after the female age of 40. Similarly, there was a significant increased OPR and decreased MR for women with a mean cycle maternal FSH of <6.4 IU/l. There was no effect of VL, CD4 count, use of HAART or time since diagnosis on the outcome. Nor was there a difference in the OPR according to paternal age, rank of attempt, cycle regime or number of follicles. Semen volume, sperm concentration, total count and progressive motility and post-wash concentration, progressive motility and total motile count inseminated were significantly higher in successful cycles. The use of frozen sperm had a significant negative impact on outcome. CONCLUSIONS This study of the potential safe and successful reproductive options available to HIV-positive men demonstrates that maternal age and semen quality, rather than HIV factors, remain the most important determinants of cycle success.

Does the cause of obstructive azoospermia affect the outcome of intracytoplasmic sperm injection: a meta-analysis.

To define whether the outcome of intracytoplasmic sperm injection (ICSI) using sperm surgically retrieved from men with obstructive azoospermia (OA) depends on the cause of obstruction.

Poor response cycles: when should we cancel? Comparison of outcome between egg collection, intrauterine insemination conversion, and follow-up cycles after abandonment

OBJECTIVE To determine optimal management with one or two mature follicles after stimulation. DESIGN Retrospective analysis. SETTING Lister fertility clinic. PATIENT(S) A total of 1,350 IVF/intracytoplasmic sperm injection cycles (7.3% of total) during 1998-2009 were found to have one or two mature follicles. INTERVENTION(S) Group 1 (n = 807) comprised those who proceeded to vaginal egg collection (VEC) (59.8%; outcome per egg collection), group 2 (n=248) those who converted to IUI (18.4%; outcome per insemination) and group 3 (n=259) those who abandoned the current cycle (21.9%; outcome per abandoned cycle in first subsequent cycle). MAIN OUTCOME MEASURE(S) Live birth rate, clinical pregnancy rate, and biochemical pregnancy rate. RESULT(S) Biochemical pregnancy rates of 13.1%, 4.9%, and 9.7%, clinical pregnancy rates of 8.1%, 3.6%, and 7.2%, and ongoing pregnancy rates of 6.8%, 2.0%, and 5.5% were achieved in groups 1, 2, and 3, respectively. All pregnancy outcomes were significantly higher after VEC (group 1) than for those converted to IUI (group 2), and all pregnancy outcomes were higher with borderline significance in group 3 vs. group 2. There was no significant difference in outcome between groups 1 and 3. CONCLUSION(S) Our data suggest that for such poor responders, proceeding to VEC may represent their best chance of successful outcome. Conversion to IUI offers the poorest outcome, and despite the potential for improvements in cycle protocol, abandoning and a further attempt does not improve outcome (using abandoned cycle as the denominator).

Assisted reproduction in the azoospermic couple.

Ten years ago, the use of donor sperm was the only option offering a realistic chance of parenting for the azoospermic or severely oligoasthenoteratozoospermic male. The first pregnancy achieved using assisted reproductive techniques in an azoospermic man was reported in 1985 following epididymal sperm aspiration in a man who had previously undergone a vasectomy. Despite this early success, in vitro fertilisation (IVF) techniques proved to be of limited use in the severely oligospermic male with a significantly reduced chance of fertilisation once the sperm count fell below <5 10/mL. However, over the last decade, the development of micromanipulation techniques and the use of surgically retrieved sperm have revolutionised the management of male factor fertility. Initial techniques, such as partial zona dissection and subzonal sperm injection (SUZI), improved outcome compared with IVF, but fertilisation rates (FR) never exceeded 20–25% and pregnancy outcome remained poor. It was not until the introduction of intracytoplasmic sperm injection (ICSI) by the work of Van Steirteghem and colleagues in Brussels that the management of male factor fertility moved significantly forward. The first pregnancies and live births after ICSI were reported in 1992 in four women who had not benefited from IVF or SUZI, and the results of a controlled comparison of SUZI and ICSI procedures on sibling oocytes showed a substantially higher normal FR with ICSI, 4% and 72%, respectively. The same authors demonstrated high fertilisation (FR) and implantation rates (IR) with ICSI in a series of 150 consecutive treatment cycles in couples previously not accepted for IVF or who had failed fertilisation with IVF. A comparative study of conventional IVF versus ICSI for patients requiring microsurgical epididymal sperm aspiration (MESA) gave overall FRs and pregnancy rates of 45% and 47%, respectively, for ICSI and 6.9% and 4.5%, respectively, for IVF. The ability of ICSI to achieve high fertilisation and pregnancy rates, regardless of semen parameters confirmed the role of ICSI in the management of azoospermic patients. In this article, we review the epidemiology, aetiology and management of azoospermia. Our overall aim is to summarise the increasing amount of published data, often contradictory, on the outcome of assisted reproduction to enable clinicians, both in a general gynaecology clinic and assisted reproduction setting, to counsel couples correctly on management options and chances of success. Epidemiology and aetiology

The effect of duration of coasting and estradiol drop on the outcome of assisted reproduction: 13 years of experience in 1,068 coasted cycles to prevent ovarian hyperstimulation

OBJECTIVE To determine the effect of duration of coasting (Cd), estradiol levels at trigger (E(2)), and level of estradiol drop (E(2)d) on live birth rate (LBR) in cycle outcome. DESIGN Retrospective analysis. SETTING Hospital-based fertility clinic. PATIENT(S) A total of 1,068 coasted cycles (5.7% of total) of IVF/ICSI from 1996 to 2008. INTERVENTION(S) Coasting in IVF/ICSI cycles. MAIN OUTCOME MEASURE(S) Live birth rate and secondary cycle outcomes. RESULT(S) Mean Cd, E(2), and E(2)d were 4.7 days, 11,567 pmol/L, and 9,760 pmol/L, respectively. Maternal age, duration of subfertility, and serum FSH were significantly lower, and AMH (39.7 vs. 15.1 pmol/L) and prevalence of polycystic ovary syndrome (31.8% vs. 17.8%) significantly higher, in coasted cycles. Fertilization rate, clinical pregnancy rate, and LBR per cycle and implantation rate of 64.4%, 40.7%, 35.7%, and 24.7%, respectively, were demonstrated, with no significant difference in LBR in cycles coasted for up to 8 days or when divided according to E(2) or E(2)d. Lack of predictive capability on LBR was confirmed by receiver operator curve analysis which demonstrated areas under the curve of 0.51, 0.53, and 0.54 for E(2), Cd, and E(2)d, respectively. CONCLUSION(S) Although cycle numbers beyond 6 days are limited, coasting for up to 8 days does not affect LBR, and E(2) and E(2)d levels do not significantly affect cycle outcome.

A decade of the United Kingdom sperm-washing program: untangling the transatlantic divide

Fertility assistance to HIV-positive men is now accepted practice in many parts of the world. We analyze the legislative, ethical, and clinical factors that explain the differences across continents with the aim of opening up the debate within the United States on whether clinics can justify denying HIV-infected men the opportunity of parenting through a now well-established risk reduction method with a proved safety record.

REVIEW: Assisted reproduction in the azoospermic couple

Ten years ago, the use of donor sperm was the only option offering a realistic chance of parenting for the azoospermic or severely oligoasthenoteratozoospermic male. The first pregnancy achieved using assisted reproductive techniques in an azoospermic man was reported in 1985 following epididymal sperm aspiration in a man who had previously undergone a vasectomy. Despite this early success, in vitro fertilisation (IVF) techniques proved to be of limited use in the severely oligospermic male with a significantly reduced chance of fertilisation once the sperm count fell below <5 10/mL. However, over the last decade, the development of micromanipulation techniques and the use of surgically retrieved sperm have revolutionised the management of male factor fertility. Initial techniques, such as partial zona dissection and subzonal sperm injection (SUZI), improved outcome compared with IVF, but fertilisation rates (FR) never exceeded 20–25% and pregnancy outcome remained poor. It was not until the introduction of intracytoplasmic sperm injection (ICSI) by the work of Van Steirteghem and colleagues in Brussels that the management of male factor fertility moved significantly forward. The first pregnancies and live births after ICSI were reported in 1992 in four women who had not benefited from IVF or SUZI, and the results of a controlled comparison of SUZI and ICSI procedures on sibling oocytes showed a substantially higher normal FR with ICSI, 4% and 72%, respectively. The same authors demonstrated high fertilisation (FR) and implantation rates (IR) with ICSI in a series of 150 consecutive treatment cycles in couples previously not accepted for IVF or who had failed fertilisation with IVF. A comparative study of conventional IVF versus ICSI for patients requiring microsurgical epididymal sperm aspiration (MESA) gave overall FRs and pregnancy rates of 45% and 47%, respectively, for ICSI and 6.9% and 4.5%, respectively, for IVF. The ability of ICSI to achieve high fertilisation and pregnancy rates, regardless of semen parameters confirmed the role of ICSI in the management of azoospermic patients. In this article, we review the epidemiology, aetiology and management of azoospermia. Our overall aim is to summarise the increasing amount of published data, often contradictory, on the outcome of assisted reproduction to enable clinicians, both in a general gynaecology clinic and assisted reproduction setting, to counsel couples correctly on management options and chances of success. Epidemiology and aetiology

A decade of the sperm-washing programme: Where are we now?

Since 1999, we have treated HIV-positive men with sperm washing as part of a risk-reduction programme with a year-on-year increase in total infectious cycles performed to over 200 in 2008. Four hundred and thirty nine cycles of IUI, 114 cycles of IVF and 117 cycles of ICSI have been performed in HIV positive men over the decade and of the 259 couples treated, a pregnancy rate and ongoing pregnancy rate per couple of 45.4% and 36.3% have been achieved with over 100 children born with no seroconversions. We outline the continued importance of such risk-reduction measures with 9.7% of samples from men with ‘stable’ disease on anti-retroviral treatment and undetectable viral load demonstrating detectable viral particles in seminal fluid and discuss measures to improve outcome in this patient group.

Frozen Embryos Generated from Surgically Retrieved Sperm from Azoospermic Men: Are They Clinically Viable?

Purpose: To assess the viability of frozen-thawed embryos derived from intracytoplasmic sperm injection (ICSI) in azoospermic men.Methods: Retrospective analysis of 154 consecutive ICSI cycles using surgically retrieved sperm from azoospermic men and case-control comparison of subsequent frozen transfer cycles with those using embryos generated from ejaculated sperm.Results: Patient and fresh cycle characteristics were similar in both groups. There were no differences between the two groups in the proportion of pronucleate (54% and 62%), and cleavage-stage embryos thawed (46% and 38%), post-thaw survival rates (retrievals: 69%; ejaculated: 73%) or quality of frozen embryos subsequently transferred. Implantation was significantly lower in frozen cycles where embryos were generated from surgically retrieved sperm (0% versus 11.5%; p=0.03). Both clinical pregnancy rate (5% versus 21%) and livebirth rate (0% versus 21%) were lower in this group, but only the difference in LBR reached borderline statistical difference (p=0.10).Conclusion: This small series demonstrates a significant impairment in implantation in FET cycles using embryos generated from surgically retrieved sperm and a trend towards a poorer pregnancy outcome.