The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET).

STUDY QUESTION: What is the association between serum progesterone levels on the day of frozen embryo transfer (FET) and the probability of live birth in women undergoing different FET regimens? SUMMARY ANSWER: Overall, serum progesterone levels <7.8 ng/ml were associated with reduced odds of live birth, although the association between serum progesterone levels and the probability of live birth appeared to vary according to the route of progesterone administration. WHAT IS KNOWN ALREADY: Progesterone is essential for pregnancy success. A recent systematic review showed that in FET cycles using vaginal progesterone for endometrial preparation, lower serum progesterone levels (<10 ng/ml) were associated with a reduction in live birth rates and higher chance of miscarriage. However, there was uncertainty about the association between serum progesterone levels and treatment outcomes in natural cycle FET (NC-FET) and HRT-FET using non-vaginal routes of progesterone administration. STUDY DESIGN SIZE DURATION: This was a multicentre (n = 8) prospective cohort study conducted in the UK between January 2020 and February 2021. PARTICIPANTS/MATERIALS SETTING METHODS: We included women having NC-FET or HRT-FET treatment with progesterone administration by any available route. Women underwent venepuncture on the day of embryo transfer. Participants and clinical personnel were blinded to the serum progesterone levels. We conducted unadjusted and multivariable logistic regression analyses to investigate the association between serum progesterone levels on the day of FET and treatment outcomes according to the type of cycle and route of exogenous progesterone administration. Our primary outcome was the live birth rate per participant. MAIN RESULTS AND THE ROLE OF CHANCE: We studied a total of 402 women. The mean (SD) serum progesterone level was 14.9 (7.5) ng/ml. Overall, the mean adjusted probability of live birth increased non-linearly from 37.6% (95% CI 26.3-48.9%) to 45.5% (95% CI 32.1-58.9%) as serum progesterone rose between the 10th (7.8 ng/ml) and 90th (24.0 ng/ml) centiles. In comparison to participants whose serum progesterone level was ≥7.8 ng/ml, those with lower progesterone (<7.8 ng/ml, 10th centile) experienced fewer live births (28.2% versus 40.0%, adjusted odds ratio [aOR] 0.41, 95% CI 0.18-0.91, P = 0.028), lower odds of clinical pregnancy (30.8% versus 45.1%, aOR 0.36, 95% CI 0.16-0.79, P = 0.011) and a trend towards increased odds of miscarriage (42.1% versus 28.7%, aOR 2.58, 95% CI 0.88-7.62, P = 0.086). In women receiving vaginal progesterone, the mean adjusted probability of live birth increased as serum progesterone levels rose, whereas women having exclusively subcutaneous progesterone experienced a reduction in the mean probability of live birth as progesterone levels rose beyond 16.3 ng/ml. The combination of vaginal and subcutaneous routes appeared to exert little impact upon the mean probability of live birth in relation to serum progesterone levels. LIMITATIONS REASONS FOR CAUTION: The final sample size was smaller than originally planned, although our study was adequately powered to confidently identify a difference in live birth between optimal and inadequate progesterone levels. Furthermore, our cohort did not include women receiving oral or rectal progestogens. WIDER IMPLICATIONS OF THE FINDINGS: Our results corroborate existing evidence suggesting that lower serum progesterone levels hinder FET success. However, the relationship between serum progesterone and the probability of live birth appears to be non-linear in women receiving exclusively subcutaneous progesterone, suggesting that in this subgroup of women, high serum progesterone may also be detrimental to treatment success. STUDY FUNDING/COMPETING INTERESTS: This work was supported by CARE Fertility and a doctoral research fellowship (awarded to P.M.) by the Tommy's Charity and the University of Birmingham. M.J.P. is supported by the NIHR Birmingham Biomedical Research Centre. S.F. is a minor shareholder of CARE Fertility but has no financial or other interest with progesterone testing or manufacturing companies. P.L. reports personal fees from Pharmasure, outside the submitted work. G.P. reports personal fees from Besins Healthcare, outside the submitted work. M.W. reports personal fees from Ferring Pharmaceuticals, outside the submitted work. The remaining authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04170517.

Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women undergoing FET. INTERVENTION(S): We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and grey literature (not widely available) from inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate. RESULT(S): Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds ≥10 ng/mL were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs. CONCLUSION(S): Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum progesterone level at the time of FET. PROSPERO NUMBER: CRD42019157071.

Preliminary investigation of the prevalence and implantation potential of abnormal embryonic phenotypes assessed using time-lapse imaging.

This retrospective, single site observational study aimed to delineate five abnormal embryonic developmental phenotypes, assessing their prevalence, development potential and suitability for inclusion in embryo selection models for IVF. In total, 15,819 embryos from 4559 treatment cycles cultured in EmbryoScope® incubators between January 2014 and January 2016 were included. Time-lapse images were assessed retrospectively for five abnormal embryo phenotypes: direct cleavage, reverse cleavage, absent cleavage, chaotic cleavage and cell lysis. The prevalence of each abnormal phenotype was assessed. Final embryo disposition, embryo quality and implantation rate were determined and compared with a control embryo cohort. The collective prevalence for the five abnormal phenotypes was 11.4%; chaotic cleavage and direct cleavage together constituted 9.7%. Implantation rates were 17.4%, 0%, 25%, 2.1% and 0% for direct, reverse, absent, chaotic cleavage and cell lysis, respectively. The overall implantation rate for all abnormal embryos with known implantation status was significantly lower compared with the control population (6.9% versus 38.7%, P < 0.0001). The proportion of good quality embryos in each category of abnormal cleavage remained below 25%. Embryos exhibiting an abnormal phenotype may have reduced developmental capability, manifested in both embryo quality and implantation potential, when compared with embryos of normal phenotype.

Examining the efficacy of six published time-lapse imaging embryo selection algorithms to predict implantation to demonstrate the need for the development of specific, in-house morphokinetic selection algorithms.

OBJECTIVE: To study the efficacy of six embryo-selection algorithms (ESAs) when applied to a large, exclusive set of known implantation embryos. DESIGN: Retrospective, observational analysis. SETTING: Fertility treatment center. PATIENT(S): Women undergoing a total of 884 in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment cycles (977 embryos) between September 2014 and September 2015 with embryos cultured using G-TL (Vitrolife) at 5% O2, 89% N2, 6% CO2, at 37°C in EmbryoScope instruments. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Efficacy of each ESA to predict implantation defined using specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristic curve (AUC), and likelihood ratio (LR), with differences in implantation rates (IR) in the categories outlined by each ESA statistically analyzed (Fisher's exact and Kruskal-Wallis tests). RESULT(S): When applied to an exclusive cohort of known implantation embryos, the PPVs of each ESA were 42.57%, 41.52%, 44.28%, 38.91%, 38.29%, and 40.45%. The NPVs were 62.12%, 68.26%, 71.35%, 76.19%, 61.10%, and 64.14%. The sensitivity was 16.70%, 75.33%, 72.94%, 98.67%, 51.19%, and 62.33% and the specificity was 85.83%, 33.33%, 42.33%, 2.67%, 48.17%, and 42.33%, The AUC were 0.584, 0.558, 0.573, 0.612, 0.543, and 0.629. Two of the ESAs resulted in statistically significant differences in the embryo classifications in terms of IR. CONCLUSION(S): These results highlight the need for the development of in-house ESAs that are specific to the patient, treatment, and environment. These data suggest that currently available ESAs may not be clinically applicable and lose their diagnostic value when externally applied.

Embryos cultured in a time-lapse system result in superior treatment outcomes: a strict matched pair analysis.

A retrospective strict matched-pair analysis of 728 treatment cycles between January 2011 and September 2014 was performed. A total of 364 treatment cycles, where all embryos were cultured and examined in EmbryoScope®, were matched to treatment cycles where all the embryos were cultured in a standard incubator with conventional morphological examination. Matching was performed for patient age, number of oocytes collected, treatment type and date of oocyte collection (± six months). The clinical (CPR), implantation (IR), live birth (LBR) and miscarriage rates (MR) were calculated and considered significant when p < 0.05 (Chi-square test). CPR, IR and LBR were found to be significantly higher in the time-lapse system (TLS) group compared to the standard incubation group (CPR = 44.8% versus 36.5%, p = 0.02; IR = 39.3% versus 32.2%, p = 0.03; and LBR = 43.1% versus 33.8%, p = 0.01). Although there was a 5.5% decrease in the MR for the TLS group when compared to the standard incubation group, this result was not statistically significant (18.9% versus 24.4%, p = 0.19). There is a paucity of well-designed studies to confirm that embryos cultured and examined in TLS can result in superior treatment outcomes, and this strict-matched pair analysis with a large cohort of treatment cycles indicates the advantage of using TLS.

Duration of luteal support after IVF is important, so why is there no consistency in practice? The results of a dynamic survey of practice in the United Kingdom.

Luteal support is considered as an essential component of IVF treatment following ovarian stimulation and embryo transfer. Several studies have consistently demonstrated a benefit of luteal support compared with no treatment and whilst a number of preparations are available, no product has been demonstrated as superior. There is an emerging body of evidence which suggests that extension of luteal support beyond biochemical pregnancy does not confer a benefit in terms of successful pregnancy outcome. We performed two surveys separated by 5 years of practice evolution, with the latter reporting on the use of luteal support in all IVF clinics in the UK. All clinics reported utilising luteal support with the majority favouring the use of Cyclogest 400 mg twice daily. In contrast, there was no consensus on the optimal duration of luteal support. Whilst 24% of clinics withdrew luteal support at biochemical confirmation of pregnancy, 40% continued treatment until 12 weeks gestation. Several clinics even extended luteal support beyond 12 weeks gestation. We observed no difference in practice based on the size of the IVF unit or treatment funding source. Although there was some change in practice between surveys in many clinics, there was no uniformity in the direction of change.

A randomized controlled clinical trial of 2295 ultrasound-guided embryo transfers.

BACKGROUND: We wanted to test the hypothesis that using abdominal ultrasound at the time of embryo transfer to guide replacement, improved pregnancy rates by at least 5%. METHODS: An RCT in a large assisted conception unit. A pilot study and power calculation suggested that at least 2000 embryo transfers were required to demonstrate a difference of 5%, for a test with 80% power and Type 1 error 0.05. Randomization, data entry and analysis were arranged independently. Randomization was stratified for age and fresh/frozen embryo transfer. Analysis was by intention to treat. RESULTS: There was no difference in clinical pregnancy or live birth rates between the two groups. The clinical pregnancy rate for ultrasound-guided embryo transfer was 22% and for non-ultrasound-guided embryo transfer was 23% (odds ratio: 0.96; 95% confidence interval: 0.79-1.18). CONCLUSIONS: We set out to determine whether ultrasound-guided embryo transfer improved clinical pregnancy rates and live birth rates in assisted conception. We used an appropriately powered RCT design. We did not demonstrate a difference. This outcome is at odds with the UKs National Institute of Clinical Excellence recommendations for fertility treatment (Fertility Assessment and Treatment for People with Fertility Problems. London, UK: RCOG Press, 2004, 112.) which used a meta-analysis of four smaller trials (range 362-800 patients, totalling 2051 embryo transfers) to conclude that ultrasound should be offered. We suggest that the current Cochrane review should be updated with data from our trial and recommend that consideration is given to accounting for heterogeneity between the included trials.

Relationship between serum human chorionic gonadotrophin levels and body mass index in women undergoing in vitro fertilisation cycles.

OBJECTIVE: To ascertain if serum concentrations following injection of human chorionic gonadotropin (hCG) influenced the outcome of in vitro fertilisation (IVF) treatment and correlated to body mass index (BMI). STUDY DESIGN: A prospective study conducted with the participation of 149 women undergoing IVF and/or intracytoplasmic sperm injection (ICSI) treatment at the regional IVF Unit in Liverpool, UK. The BMI of each individual was calculated and serum hCG concentrations were measured at 12 and 36 h following a subcutaneously (SC) injection of 5000 IU hCG. The main outcome measures were fertilisation rate and biochemical pregnancy rate. RESULTS: No correlation was found between serum hCG levels at 12 and 36 h with the number of oocytes retrieved or the number of oocytes fertilised. Furthermore, there was no correlation between BMI and hCG levels at 12 and 36 h following administration (Pearson's correlation coefficient: -0.23, -0.24, respectively). CONCLUSION: Our results suggest that the serum concentrations of hCG do not influence IVF outcome and that the serum levels of hCG achieved following administration do not correlate with the individual's BMI. Serum hCG concentration also does not correlate with number of oocytes collected or fertilisation rate.

Seasonal variation in assisted conception cycles and the influence of photoperiodism on outcome in in vitro fertilization cycles.

The effect of seasonality and daylight length on mammalian reproduction leading to spring births has been well established, and is known as photoperiodism. In assisted reproduction there is much greater uncertainty as to the effect of seasonality. This was a 4-year retrospective analysis of 2709 standardised cycles of IVF/ICSI. Data was analysed with regard to the 1642 cycles occurring during the months of extended daylight (Apr-Sept) and those 1067 cycles during winter months of restricted light length (Oct-Mar). The results showed that there was significant improvement in assisted conception outcomes in cycles performed in summer (lighter) months with more efficient ovarian stimulation 766iu v880iu/per oocyte retrieved (p=0.006). There was similarly a significantly improved implantation rate per embryo transferred 11.42% vs 9.35% (p=0.011) and greater clinical pregnancy rate 20% vs 15% (p=0.0033) during summer cycles. This study appears to demonstrate a significant benefit of increased daylight length on outcomes of IVF/ICSI cycles. Whilst the exact mechanism of this is unclear, it would seem probable that melatonin may have actions at multiple sites and on multiple levels of the reproductive tract, and may exert a more profound effect on outcomes of assisted conception cycles than has been previously considered.

Gynaefix frameless IUD: Cause of bowel resection.

A case of a lost GyneFix intrauterine contraceptive device (IUD) is described, in which laparoscopy failed to identify the device and laparotomy had to be carried out to remove the IUD, which was embedded in the small bowel necessitating bowel resection. Awareness of this complication is necessary, and advanced training is required in order to minimize risks. A description of the GyneFix device, the possible adverse effects and incidence of complications, the importance of post-insertion follow-up, and the need for awareness of the possibility of migration through the bowel are discussed.

Do lunar phases affect conception rates in assisted reproduction?

OBJECTIVES: To assess the effect of the phases of the moon on pregnancy rates in humans following in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Retrospective, observational study. SETTING: Reproductive Medicine Unit, Liverpool Women's Hospital. PATIENT: Complete data for all women undergoing assisted conception procedures over a period of 13 years (1995-2002). INTERVENTION: Assisted conception procedures--IVF and ICSI. MAIN OUTCOME MEASURES: Biochemical pregnancy that is positive pregnancy test result following embryo transfer. RESULTS: There was no significant effect of any lunar phase on the incidence of biochemical pregnancy (p-value 0.71). Age of the woman significantly affects the chances of pregnancy, (OR 0.95, 95% CI 0.91, 0.998, and p-value 0.04). The chances of pregnancy rises significantly with increase in the number of embryos replaced from 1 to 2 (OR 2.97, CI 1.36, 6.48, and p-value 0.01). CONCLUSION: Pregnancy rates in humans, following assisted conception, appears to be independent of the effect of the lunar phase during which embryo transfer is carried out.

Effects of supra-physiological changes in human ovarian hormone levels on maximum force production of the first dorsal interosseus muscle.

The purpose of this study was to investigate the effects of supra-physiological changes in ovarian hormone levels on maximum force production in two conditions, one physiological (pregnancy) and one pseudo-physiological (in vitro fertilization (IVF) treatment). Forty IVF patients were tested at four distinct stages of treatment and 35 women were tested during each trimester of pregnancy and following parturition. Maximum voluntary isometric force per unit cross-sectional area of the first dorsal interosseus muscle was measured. Plasma concentrations of total and bioavailable oestradiol and testosterone were measured, in addition to the total concentrations of progesterone and human chorionic gonadotropin. Despite significant changes in the concentrations of total progesterone, 17beta-oestradiol, bioavailable oestradiol and testosterone between phases, strength did not change significantly throughout IVF treatment (1.30+/-0.29, 1.16+/-0.38, 1.20+/-0.29 and 1.26+/-0.34 N mm-2, respectively, in the 4 phases of IVF treatment). Force production was significantly higher during the second trimester of pregnancy than following childbirth (1.33+/-0.20 N mm-2 at week 12 of pregnancy, 1.51+/-0.42 N mm-2 at week 20, 1.15+/-0.26 N mm-2 at week 36 and 0.94+/-0.31 N mm-2 at week 6 postnatal) but was not significantly correlated with any of the hormones measured. These data suggest that extreme changes in the concentrations of reproductive hormones do not affect the maximum force-generating capacity of young women.

NHS funded fertility treatment--a national service in name only?

The variable nature of NHS provision of fertility services has again been highlighted by the response of commissioners to the recent guidance from the National Institute of Clinical Excellence. This paper describes an evidence-based model for policy aimed at minimising inequity across one Strategic Health Authority. The paper highlights the difficulties resulting from the current Department of Health guidance on targeting those in greatest need. A different way of describing this group is proposed, namely, defining childlessness in terms of parental status alone. This is clear to both patient and clinician at the outset, not subject to variable interpretation and because it is quantifiable for any given population, facilitates the commissioning of a level of service provision that reflects expressed need. A clinical audit suggests that the annual incidence of fertility problems prompting attendance at secondary care clinics is similar to levels observed nearly 20 years ago, at around 98 per 10,000 of the fertile population (proxy denominator, women aged 25 - 39). Our model further indicates that, for the more complex treatments, if both partners were required to be childless and treatments were to be delivered within 12 - 18 months of listing, commissioners would need to fund treatment for around 15 - 20 patients per 10,000 of the fertile population. If only one partner was required to be childless this figure would rise by 15 - 20%. We argue that despite the clinical guidelines, fertility treatments will remain a 'postcode lottery' unless central government addresses the priority to be given to fertility treatment on a national basis.

National survey of current practice in assessing tubal patency in the UK.

We conducted a postal survey to find out the current practice in the UK regarding the methods employed to assess tubal patency. A questionnaire was developed to evaluate the methods used to assess tubal patency in women presenting with infertility with or without risk factors suggesting pelvic disease. A total of 496 questionnaires were sent and 174 responded (35%). The survey represented an overall view as both gynaecologists and radiologists from secondary and tertiary centres responded. In the responses from radiologists, a hysterosalpingogram was the investigation of choice for both low risk (61%) and high risk women (50%). However in the responses from gynaecologists, in patients with no past gynaecological history, the majority performed a hysterosalpingogram (58%) or hystero contrast sonography (HyCoSy) (14%) whereas in patients in whom pelvic pathology was suspected, most (84%) performed a laparoscopy and dye test. The survey also showed that HyCoSy was performed in only a few centres in the UK. The responses from the majority of gynaecologists were in accordance with the RCOG guidelines. However, still some centres (28%) offered laparoscopy and dye test in low risk women as the primary test for assessing tubal patency. Given the risks associated with laparoscopy, this should be reserved for cases where pathology is suspected and scheduled to be combined with laparoscopic surgery.

The ratio of second to fourth digit length in azoospermic males undergoing surgical sperm retrieval: predictive value for sperm retrieval and on wubsequent fertilization and pregnancy rates in IVF/ICSI cycles.

The differentiation of the urogenital system and the appendicular skeleton in vertebrates is under the control of Homeobox (Hox) genes. It has been shown that this common control of digit and gonad differentiation has connected the pattern of digit formation to spermatogenesis and prenatal hormone concentrations in males. We wished to establish whether digit patterns, particularly the ratio between the lengths of the second and fourth digit in males (2D : 4D), was related to spermatogenesis and, more specifically, the presence of spermatozoa in testicular biopsies from azoospermic men undergoing surgical sperm retrieval. Forty-four men were recruited, of whom 16 were diagnosed with nonobstructive azoospermia and 4 with congenital bilateral absence of the vas deferens, and 24 previously fertile men were azoospermic after previous vasectomy. Our results show that men with previous fertility or of an acquired form of azoospermia had significantly lower 2D : 4D ratios than men with nonobstructive azoospermia. In nonobstructive azoospermia, there was a significantly lower 2D : 4D ratio on the left side in men who had successful retrieval than those with unsuccessful retrieval. For these men who had a successful retrieval, none had a 2D : 4D ratio more than 1 on the left side, whereas 4 of 7 men in whom sperm was not found had a 2D : 4D ratio greater than 1. On successful sperm retrieval, subsequent fertilization and clinical pregnancy rates were unaffected by 2D : 4D ratios.

Endometrial integrin expression in women undergoing in vitro fertilization and the association with subsequent treatment outcome.

OBJECTIVE: To study the endometrial expression of three integrins (alpha v beta 3, alpha 4 beta 1, and alpha 1 beta 1) in women undergoing IVF-intracytoplasmic sperm injection (ICSI) treatment and assess whether they could be used to predict subsequent treatment success.Prospective observational study. Healthy volunteers in a large teaching hospital. PATIENT(S): Sixty-six patients attending for IVF-ICSI treatment. INTERVENTION(S): Timed endometrial biopsies were taken, during the implantation window at LH + 7-9 days, from women before IVF-ICSI treatment. MAIN OUTCOME MEASURE(S): Histological dating of endometrium and immunohistochemical staining intensity of alpha 4 beta 1, alpha v beta 3, and alpha 1 beta 1 integrins. The integrin levels were correlated with subsequent success rates. RESULT(S): There was a statistically significantly greater expression of alpha v beta 3 in the luminal epithelium of those patients who had successful treatment. However, treatment was successful in some patients with negative expression. CONCLUSION(S): Integrins are important markers of endometrial receptivity. There is an association between an in-phase endometrial biopsy, with positive luminal alpha v beta 3 integrin expression, and subsequent treatment success. However, the clinical value of assessing the endometrium before treatment has drawbacks, and further work needs to be done before this can be considered a clinically useful test.

A potential new use for gonadotropin-releasing hormone antagonists.

OBJECTIVE: To describe a potential new use of gonadotropin-releasing hormone (GnRH) antagonists. DESIGN: Case report. SETTING: Assisted conception unit at a teaching hospital in the United Kingdom. PATIENT(S): A 37-year-old woman undergoing in vitro fertilization (IVF) who accidentally stopped using GnRH agonists after starting ovarian stimulation. INTERVENTION(S): A GnRH antagonist was used to avoid a luteinizing hormone (LH) surge and hence "rescue" the cycle. RESULT(S): Successful oocyte retrieval was carried out, two embryos transferred, and a viable twin pregnancy ensued. CONCLUSION(S): This may be a new indication for the use of GnRH antagonists.

Optimal treatment for poor responders to ovarian stimulation: does in vitro insemination offer any advantages to intrauterine insemination?

A retrospective study was performed of 1832 consecutive in vitro insemination (IVF)/intracytoplasmic sperm injection (ICSI) cycles over 18 months, to analyse the benefits or otherwise to the patient of continuing with in vitro treatment or converting the assisted conception cycle to intrauterine insemination (IUI). Two hundred and seventy cycles were identified in which three follicles or fewer were obtained after controlled ovarian hyperstimulation; in 143 of these cycles, the clinicians or patients elected to abandon all treatment, whereas treatment was continued in 127 patients. In 79 cycles, the patients proceeded with IVF/ICSI and in 48 patients, the cycles were converted to IUI. Data were analysed with regard to the clinical pregnancy rate. In addition, the data for IUI were compared with eight cycles of supraovulation IUI (S/IUI) performed over the same period. There were no significant differences in clinical pregnancy rates among any treatment modality 6/48 (12.5%), 6/79 (7.7%) and 1/8 (12.5%) for IUI, IVF and S/IUI, respectively (P = 0.64). The lowest total number of motile spermatozoa required to achieve pregnancy using IUI was 2.0 x 10(6). In conclusion, it appears that, if the treatment is suitable, patients who respond poorly to controlled hyperstimulation for IVF would not be disadvantaged in achieving a pregnancy by offering them conversion to the medically and financially less interventional IUI.

Postoperative pain, complications, and satisfaction rates in patients who undergo surgical sperm retrieval.

OBJECTIVE: To determine patients' experiences with surgical sperm retrieval and its common complications. DESIGN: A questionnaire based survey using visual analogue scales (VAS) and closed questions to analyze complication, pain, and satisfaction rates. SETTING: Tertiary care university hospital. PATIENT(S): One hundred consecutive males undergoing surgical sperm retrieval by percutaneous epididymal sperm aspiration (PESA) or testicular sperm extraction (TESE). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We surveyed for pain perception complication rates and satisfaction scores. RESULT(S): Of the 85 patients who replied, 21 underwent retrieval for nonobstructive causes, 37 following failed reversal of vasectomy, and 27 for other obstructive causes. Retrieval was successful in 100% of obstructive causes and in 61% for nonobstructive azoospermia. Epididymal retrieval was successful in 23 patients, 30 patients underwent TESE after failed PESA, and 23 had TESE only. There were significant increases in pain perception scores and reported complications with TESE over PESA (31 vs. 16; and 21 out of 63 vs. 2 out of 22, respectively), but no difference in satisfaction rate. The cause of azoospermia did not affect pain perception or satisfaction in TESE. Complication rates were increased in larger testes (3 out of 22 vs. 24 out of 63). Unsuccessful sperm retrieval did not significantly affect patients' pain perception or satisfaction. Surgical sperm retrieval was rated as significantly less painful than both vasectomy and reversal (21% vs. 42% vs. 57%, respectively) and was associated with significantly fewer days absent from work (3.0 vs. 8.5). CONCLUSION(S): Surgical sperm retrieval by PESA or TESE is a safe procedure with only minor complications that is tolerated well by patients.

Effect on clinical outcome of the interval between collection of epididymal and testicular spermatozoa and intracytoplasmic sperm injection in obstructive azoospermia.

We wished to determine whether the interval between surgical retrieval of epididymal and testicular spermatozoa in obstructive azoospermia and their subsequent use in intracytoplasmic sperm injection (ICSI) has an effect on their fertilizing capacity and pregnancy rates in patients undergoing ICSI. This was a retrospective review of 164 consecutive cycles of ICSI in partners of men undergoing surgical sperm retrieval for obstructive azoospermia. Seventy-three cycles used fresh testicular spermatozoa; in 35 cycles ICSI was performed within 4 hours of sperm retrieval, and in 38 cycles spermatozoa were incubated overnight before ICSI. Epididymal spermatozoa were used in 29 cycles; 22 cases within 4 hours of retrieval and 7 cases following overnight culture. Cyropreserved testicular and epididymal spermatozoa were used in 42 and 20 ICSI cycles, respectively. Fertilization and clinical pregnancy rates were calculated for each treatment group. Fertilization rates for epididymal spermatozoa were 67% at 4 hours, 56% at 24 hours, and 63% for cryopreserved spermatozoa (P =.52). Fertilization rates for testicular spermatozoa were 63% at 4 hours, 71% at 24 hours, and 60% for cryopreserved spermatozoa (P =.16). Unlike testicular spermatozoa, cryopreserved epididymal spermatozoa showed a significant increase in clinical pregnancy rates with cryopreservation, with rates of 4 of 22, 1 of 7, and 10 of 20 at 4 hours, 24 hours, and cryopreservation, respectively (P =.049). This study confirms that fertilization and pregnancy rates following ICSI with motile spermatozoa are unaffected by the duration between surgical retrieval of spermatozoa and their injection into oocytes. It also demonstrates that of all treatment modalities, the use of frozen epididymal spermatozoa was associated with the greatest pregnancy rates.