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.

Cystic fibrosis screening in assisted reproduction.

PURPOSE OF REVIEW: The purpose of this review is to discuss the incidence of cystic fibrosis in the general population, in ethnically diverse populations and specifically in couples needing assisted reproduction caused by male factor subfertility. We review the current understanding of risks for reproductive couples and discuss ideal screening strategies. RECENT FINDINGS: In ethnically diverse populations, a large difference in clinical sensitivity and birth prevalence exists between the broad racial/ethnic groups examined. Extensive data clearly demonstrate the cost-effectiveness of cystic fibrosis screening. Testing for cystic fibrosis gene mutations is reliable and, with a 26-mutation panel, nearly 90% of possible severe mutations can be detected. To halve the incidence of cystic fibrosis in the community, by offering genetic testing of the fetus if both partners are carrier positive, may also be possible. SUMMARY: Recent guidelines suggest that all couples contemplating pregnancy should be informed of molecular screening for cystic fibrosis carrier status for purposes of genetic counselling. In ethnically diverse populations, ethnic-specific mutations should be included in the mutation panels.

Novel association between sperm deformity index and oxidative stress-induced DNA damage in infertile male patients.

AIM: To investigate the impact of abnormal sperm morphology using the sperm deformity index (SDI) on reactive oxygen species (ROS) production and its correlation with sperm DNA damage. METHODS: Semen samples were collected from men undergoing infertility screening (n = 7) and healthy donors (n = 6). Mature spermatozoa were isolated and incubated with 5 mmol/L beta-nicotinamide adenine dinucleotide phosphate (NADPH) for up to 24 h to induce ROS. Sperm morphology was evaluated using strict Tygerberg's criteria and the SDI. ROS levels and DNA damage were assessed using chemiluminescence and terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL) assays, respectively. RESULTS: SDI values (median [interquartiles]) were higher in patients than donors (2 [1.8, 2.1] vs. 1.53 [1.52, 1.58], P = 0.008). Aliquots treated with NADPH showed higher ROS levels (1.22 [0.30, 1.87] vs. 0.39 [0.10, 0.57], P = 0.03) and higher incidence of DNA damage than those not treated (10 [4.69, 24.85] vs. 3.85 [2.58, 5.10], P = 0.008). Higher DNA damage was also seen following 24 h of incubation in patients compared to donors. SDI correlated with the percentage increase in sperm DNA damage following incubation for 24 h in samples treated with NADPH (r = 0.7, P = 0.008) and controls (r = 0.58, P = 0.04). CONCLUSION: SDI may be a useful tool in identifying potential infertile males with abnormal prevalence of oxidative stress (OS)-induced DNA damage. NADPH plays a role in ROS-mediated sperm DNA damage, which appears to be more evident in infertile patients with semen samples containing a high incidence of morphologically abnormal spermatozoa.

Novel associations between specific sperm morphological defects and leukocytospermia.

OBJECTIVE: To examine the relationship between leukocyte concentrations in semen and sperm morphology in a group of infertile men and healthy fertile donors. DESIGN: A prospective clinical study. SETTING: Male infertility clinic at a tertiary care teaching hospital and a reproductive medicine unit at a Women's Hospital in the United Kingdom. PATIENT(S): Fifty-six infertile men and 13 healthy fertile sperm donors (control). INTERVENTION(S): Standard semen analysis, seminal leukocyte concentration, and the assessment of sperm morphology and sperm deformity index (SDI), applying Tygerberg's strict criteria. MAIN OUTCOME MEASURE(S): Granulocyte concentrations in semen, percentages of different sperm morphological abnormalities, and SDI scores. RESULT(S): Leukocyte concentrations were statistically significantly and negatively correlated with the proportion of sperm with damaged acrosomes, cytoplasmic droplet, tail defects, and SDI scores with normal and borderline morphology. The percentage sperm motility was significantly and negatively correlated with leukocytic concentration in semen. However, the leukocytic concentration was not significantly correlated with sperm concentration. CONCLUSION(S): This is the first study to report a significant positive correlation between leukocytospermia and sperm tail defects, acrosomal damage, and high SDI scores. These observations suggest that leukocytospermia is associated with compromised sperm structural integrity.

Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index.

OBJECTIVE: To examine the relationship between sperm reactive oxygen species (ROS) production and sperm morphology in a group of infertile men and healthy fertile donors. DESIGN: A prospective clinical study. SETTING: Male infertility clinic, Glickman Urological Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, and the Reproductive Medicine Unit, Liverpool Women's Hospital, United Kingdom PATIENT(S): Thirty-nine infertile men and 13 healthy fertile donors (control). INTERVENTION(S): Standard semen analysis, seminal leukocyte concentration, assessment of sperm morphology, and measurement of sperm ROS production. MAIN OUTCOME MEASURE(S): Levels of sperm ROS production, percentages of different sperm morphological abnormalities, and the sperm deformity index (SDI) scores. RESULT(S): A significant negative correlation was observed between sperm ROS production and the proportion of sperm with normal morphology and borderline morphology. Reactive oxygen species production was positively correlated with the proportion of sperm with amorphous heads, damaged acrosomes, midpiece defects, cytoplasmic droplets, tail defects, and SDI scores. Logistic regression analysis identified a two-variable model including SDI and percentage sperm motility, which correctly identified 84% of individuals with high seminal ROS and 85% of individuals with low seminal ROS. The model had an overall accuracy of 85%. CONCLUSION(S): The standard semen analysis to assess sperm motility, sperm morphology, and the SDI scores is a useful tool in identifying infertile men with high seminal ROS in infertility clinics where facilities for measuring levels of seminal ROS are not available.

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.

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.

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.

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.

Sperm chromosomal abnormalities are linked to sperm morphologic deformities.

OBJECTIVE: To describe the association between specific sperm morphologic abnormalities and sperm chromosomal abnormalities on multicolor interphase fluorescence in situ hybridization (FISH). DESIGN: Case report. Reproductive medicine unit in a tertiary referral center. PATIENT(S): Three infertile men with severe oligoasthenospermia and total teratozoospermia who were referred for IVF treatment. MAIN OUTCOME MEASURE(S): Incidence of spermatozoal chromosomal aneuploidy for chromosome 18 and the sex chromosomes by using FISH. RESULT(S): Morphologic assessment of sperm revealed a high incidence of double heads, multinucleated sperm heads, and multiple tails. Hormone profiles and karyotyping of peripheral lymphocytes were normal in the three men. The proportion of sperm with disomy, trisomy and tetrasomy for chromosome 18, and the sex chromosomes in each patient was 100%, 76%, and 82.5%, respectively. CONCLUSION(S): Specific morphologic abnormalities of sperm may be associated with higher incidence of chromosomal abnormalities. Resolving infertility by offering patients in vitro fertilization/intracytoplasmic sperm injection must be approached with caution because of the significant risk for embryonic aneuploidy and chromosomal abnormalities in any subsequent offspring.

The value of routine estradiol monitoring in assisted conception cycles.

BACKGROUND: Traditional monitoring of an in vitro fertilization (IVF) treatment cycle includes regular estradiol levels and ultrasound scans in an attempt to reduce the risk of ovarian hyperstimulation syndrome (OHSS). The need for estradiol monitoring remains controversial. METHODS: We reviewed 538 consecutive cycles of IVF that were carried out in our unit to ascertain whether routine estradiol monitoring was of help in preventing OHSS and could be used to predict treatment outcome. Two hundred and sixty-eight patients had their ovarian response monitored with ultrasound (USS) and estradiol levels on the day of hCG administration. The following 270 had USS monitoring but only had an estradiol level checked if they were deemed to be at high risk of OHSS (> 20 follicles on USS or symptomatic). RESULTS: Pregnancy rates per treatment cycle and per embryo transfer were similar in the two groups (all p > 0.05). There were two patients in each group requiring admission to hospital for OHSS. CONCLUSIONS: Estradiol levels did not correlate with IVF outcome. In summary therefore estradiol levels are a poor predictor of treatment success and done routinely do not reduce the incidence of OHSS. It is only necessary to measure the estradiol level in those patients at risk of OHSS on USS monitoring.

Reproductive potential of fresh and cryopreserved epididymal and testicular spermatozoa in consecutive intracytoplasmic sperm injection cycles in the same patients.

OBJECTIVE: To determine if the cryopreservation of epididymal and testicular spermatozoa alters their reproductive potential by examination of patients who underwent consecutive cycles of ICSI using fresh and then cryopreserved spermatozoa. DESIGN: Retrospective review. SETTING: Tertiary care university hospital. PATIENT(S): One hundred sixty-two consecutive cycles of ICSI were analyzed. Thirteen patients were identified as having undergone treatment with freshly retrieved epididymal spermatozoa; these patients subsequently underwent treatment with spermatozoa cryopreserved from that cycle. Eighteen patients underwent ICSI with freshly retrieved testicular spermatozoa; these patients subsequently underwent treatment with spermatozoa cryopreserved from that cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization rates and pregnancy rates. RESULT(S): The fertilizing capacity of epididymal spermatozoa remained unchanged after cryopreservation and subsequent thawing, with fertilization rates of 58% and 57% for fresh and cryopreserved spermatozoa, respectively. Testicular spermatozoa, however, showed a significant decrease in fertilizing capacity after cryopreservation when compared with freshly retrieved spermatozoa (52% and 71%, respectively). Pregnancy rates appeared unaffected by the cryopreservation of epididymal spermatozoa (fresh, 3/13; frozen, 2/13) or testicular spermatozoa (fresh, 2/18; frozen, 5/18). CONCLUSION(S): This study offers further evidence that motile epididymal spermatozoa retain their fertilizing capacity after cryopreservation. The data presented on testicular spermatozoa suggest that although cryopreservation may reduce the fertilizing capacity of testicular spermatozoa, there is no decrease in pregnancy rates.

Surgical sperm retrieval: a review of current practice.

Although pregnancies were achieved after surgical sperm retrieval and in vitro fertilization 8 years before the introduction of intracytoplasmic sperm injection (ICSI), it is the development of ICSI that has led to the rapid expansion of surgical procedures to obtain sperm from azoospermic males for use in assisted conception cycles. The natural desire for couples to achieve a pregnancy using their own gametes and a national shortage of donor sperm have driven the demand for an expansion of this service. Males who have previously been considered unable to father their own genetic child can now be offered treatment, which, in most cases, will lead to the recovery of sperm for use in treatment. This article considers the development of the techniques available to clinicians and provides an overview of the many treatments (and their acronyms) to assist clinicians unfamiliar with the practicalities of surgical sperm retrieval. In reviewing the current published studies, we also offer some guidelines as to the optimization of the potential future provisions of surgical sperm retrieval treatments for azoospermic males, either secondary to obstruction (particularly after vasectomy) or from non-obstructive causes.