The possible influence of increased body mass index on the clinical efficacy of standard human chorionic gonadotropin dosage.

OBJECTIVES: To evaluate whether the efficacy of standard (10,000 IU) hCG dosage is BMI dependent. PATIENTS & METHODS: During the study period, body mass index (BMI) was recorded in 261 consecutive women enrolled in our ICSI program. Women in the 90th BMI percentile were compared with those in the 10th percentile. The number and percent of mature metaphase-II (M-II) oocytes were considered as the outcome measure. RESULTS: Mean BMI of the 10th and 90th percentile groups were 18.2 +/- 0.7 kg/m2 (n = 26) and 32.8 +/- 2.2 kg/m2 (n = 27), respectively. There were no differences between the groups in mean patients age, number of gonadotropin ampoules used, mean number of oocytes retrieved or the number and percentage of mature M-II oocytes. CONCLUSIONS: Standard (10,000 IU) hCG dosage is adequate to induce final oocyte maturation in IVF patients regardless of their BMI. This may imply that this hCG dosage is much higher than the dosage that is actually required.

Comparison of embryo quality between intracytoplasmic sperm injection and in vitro fertilization in sibling oocytes.

BACKGROUND: The aim of the present study was to compare the quality of embryos derived from sibling oocytes by in vitro fertilization (IVF) or ICSI. METHODS: Consecutive patients with a less than 40% fertilization rate in a previous standard IVF cycle or with relative male factor infertility were recruited for the study. The oocytes retrieved from each patient were divided into two groups for either conventional insemination (group A) or ICSI (group B). Power analysis showed that to detect a 25% difference in the rate of high-quality embryos between the groups with a power of 0.8, at least 1,200 oocytes were needed in each group. RESULTS: One hundred seventy-seven patients were included in the study. Group A was comprised of 1,526 oocytes and group B of 1,480 sibling oocytes. As expected, the fertilization rate was significantly higher in group B than group A (67.1 vs. 43.6%, p < 0.001). No significant between-group differences were observed in cleavage rate (92.7 and 89.7%, respectively) and the rate of either grade A embryos (22.6 and 23.9%, respectively) or grade A(1) embryos (37.3 and 33.5%, respectively). However, in the subgroup of patients with relative male-factor infertility (n = 36), the rate of grade A(1) embryos was significantly higher in the IVF than the ICSI group (46.4 vs. 29.0%, respectively, p = 0.02). CONCLUSIONS: Embryo quality does not seem to be influenced by the mode of fertilization (IVF or ICSI). We assume that embryo quality depends on intrinsic factors of the gametes involved rather than on the fertilization process per se.

Effect of contaminated preprocessed semen on fertilization rate and embryo quality in assisted reproductive techniques.

We aimed to identify the sources and prevalence of semen contamination from mastrubation and determine the effect of bacterospermia on fertilization rate and embryo quality in standard in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). This was a prospective controlled study, in an IVF unit of a university teaching hospital, of 93 consecutive couples undergoing IVF-embryo transfer cycles. We evaluated handwashing; semen collection and processing; and assisted reproductive technology using semen provided by masturbation. The main outcome measures were presence and type of micro-organisms in the semen samples and embryo culture medium; the effect of hand washing on rate of contamination; and the effect of semen contamination on fertilization rate and embryo quality. The first consecutive 52 men of the 93 couples were not instructed to wash their hands before masturbation, and the remainder were so instructed. Forty-nine semen cultures (94.2%) in the first group were contaminated compared to only 16 (39%) in the second (p < 0.016); 27 of the 65 positive cultures (41.5%) were contaminated by more than one organism. The most common contaminators were bacteria usually found on the skin. All but four embryo medium cultures were negative. There was no significant difference in fertilization rate and embryo quality by culture findings in either the IVF or the ICSI procedures. We found that a high percentage of manually obtained semen for standard IVF or ICSI procedures was contaminated, but this had no effect on fertilization rate and embryo quality.

Results of in vitro fertilization cycles in women aged 43-45 years.

Our objective was to evaluate the results of in vitro fertilization (IVF) cycles in the elderly (43-45 years old) female population. All consecutive women aged 43-45 years admitted to our IVF unit from January 1996 to December 2001 were enrolled in the study. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred and pregnancy rate were assessed. Seven hundred and eight consecutive IVF cycles in 276 patients were evaluated. Two hundred and seven cycles were cancelled (cancellation rate 29.2%). Forty-seven patients achieved a clinical pregnancy (pregnancy rate 6.6% per cycle and 9.4% embryo transfer) with a 30% live birth rate. In patients who underwent embryo transfer, there were no differences between conception and non-conception cycles in patient's age, number of gonadotropin ampules used, length of ovarian stimulation, number of oocytes retrieved, fertilization rate or cleavage rate. However, the conception cycles were associated with a significantly lower peak estradiol level (p < 0.04) and higher number of total (p < 0.03) and good-quality (p < 0.005) embryos transferred, in addition to a lower ratio of estradiol level/number of follicles > 14 mm on day of human chorionic gonadotropin administration and of estradiol level/number of oocytes retrieved. We conclude that, although older female age is a major contributor to IVF failure, successful IVF cycles can be expected in patients aged 43-45 years in the presence of low ratios of peak estradiol to either number of follicles > 14 mm on day of human chorionic gonadotropin administration or number of oocytes retrieved that reach the stage of embryo transfer with at least two good-quality embryos.

Acute liver failure as the sole manifestation of relapsing non-Hodgkin's lymphoma.

Acute liver failure due to hepatic involvement by haematological malignancies is very rare, and usually has a rapidly fatal prognosis. We describe the case of a man who was treated for diffuse large B-cell lymphoma, and achieved a complete remission after eight courses of chemotherapy. He then presented with acute liver failure. Transjugular liver biopsy revealed massive infiltration by lymphomatous cells, with extensive necrosis. A CT scan did not show any evidence of extrahepatic lymphoma. The patient recovered from the liver failure following combined immuno-chemotherapy. Recurrence of the disease should be included in the differential diagnosis of patients with haematological malignancies and acute liver failure, even without evidence of extrahepatic involvement.

Controlled ovarian hyperstimulation--a state of endothelial activation.

PROBLEM: To aim of the study was to investigate whether controlled ovarian hyperstimulation (COH) causes endothelial activation and whether there is a correlation between endothelial activation and serum sex-steroid levels. METHOD OF STUDY: The study population consisted of 14 consecutive patients undergoing our routine IVF long gonadotropin-releasing hormone-analog protocol. Blood was drawn three times during the COH cycle: (1) day when adequate suppression was obtained (Day-S); (2) on the day of or the day prior to hCG administration (Day-hCG); and (3) on the day of ovum pick-up (Day-OPU). The levels of sex steroids and plasma soluble endothelial (E)-selectin were compared among the time points. Soluble E-selectin was measured with a commercial sandwich enzyme-linked immunosorbent assay. RESULTS: Soluble E-selectin levels were significantly higher on Day-OPU than Day-S and Day-hCG, whereas no difference was observed between Day-hCG and Day-S. No significant correlations were found between soluble E-selectin level and patient age, number of gonadotropin ampoules used, number of oocytes retrieved, or serum estradiol, progesterone and human chorionic gonadotropin levels. CONCLUSIONS: Human chorionic gonadotropin administration leads to endothelial activation regardless of the degree of ovarian response. Further studies are required to elucidate the relationship between COH and endothelial activation. These findings may lead to new strategies for predicting and preventing complications of COH, such as severe ovarian hyperstimulation syndrome.

Natural-cycle in vitro fertilization in women aged over 44 years.

Women who are 44 years of age or more are usually denied infertility treatment because of their low response to ovarian stimulation and the extremely low pregnancy rate that can be achieved. The object of this study was to assess the place of natural-cycle in vitro fertilization (IVF) in this population. From January 1996 to September 1997, all consecutive women aged 44-47 years who approached our unit seeking infertility treatment with their own oocytes were enrolled in the study. After a counselling session in which the advantage of egg donation was discussed, women who still wished to try to conceive by utilizing their own oocytes were treated according to the following protocol. Ultrasound and hormonal surveillance was carried out starting 5 days prior to the presumed ovulation day, based on previous menstrual history. Ovum pick-up was timed either by detection of the luteinizing hormone surge or by human chorionic gonadotropin administration. In total, 48 treatment cycles were conducted in 20 women. Oocyte retrieval was successful in 22 cycles. Fertilization and cleavage rates of 48% and 100%, respectively, were detected. Nine of the 12 embryos transferred were defined as grade A. One chemical and one ongoing pregnancy were achieved. We conclude that, despite the fact that high-quality embryos can be obtained in this population, the likelihood of pregnancy is low.

Pregnancy potential of embryos from in vitro fertilization compared to intracytoplasmic sperm injection.

The aim of this study was to investigate whether equally high-quality embryos derived from standard in vitro fertilization (IVF) or from intracytoplasmic sperm injection (ICSI) differ in pregnancy potential. We evaluated all consecutive cycles from January 1996 to December 1997, in which only high-quality embryos were transferred. A total of 171 IVF and 148 ICSI cycle procedures, conducted in 153 and 130 women respectively, met with the inclusion criteria. A higher clinical pregnancy rate was recorded for the IVF group than the ICSI group (35% versus 29% respectively), although the difference did not achieve statistical significance. This result was detected despite the significantly higher mean age of the IVF patients compared with the ICSI patients (35 +/- 4.9 years and 33 +/- 5.2 years respectively). Controlling for the effect of patient age using linear regression analysis yielded a significantly higher clinical pregnancy rate for IVF therapy. In conclusion, IVF is associated with a significantly higher clinical pregnancy rate than ICSI even when high-quality, morphologically comparable embryos are utilized.

Double (consecutive) transfer of early embryos and blastocysts: aims and results.

OBJECTIVE: The aim of this study was to evaluate the consecutive transfer approach of early embryos and blastocyst(s). DESIGN: Case-control study. SETTING: Public assisted reproduction technology unit. PATIENT(S): The study population consisted of three groups. In Group 1, a double transfer was performed on 136 consecutive women, that is, a standard transfer of embryos on day 2 or 3, and a second transfer of a blastocyst(s). In Group 2, an early transfer of only two embryos and a second transfer of one blastocyst were performed on 29 women from group 1 who had more than three high-quality embryos available for early transfer. In Group 3, a single early transfer was performed on 139 consecutive women who received three high-quality embryos (controls). INTERVENTION(S): Early embryo transfer, extended culture of the spare embryos, and a second transfer of a blastocyst(s). MAIN OUTCOME MEASURE(S): Implantation and pregnancy rates. RESULTSs): No differences were detected among the three groups in either pregnancy or implantation rates (pregnancy: 36.8%, 41.4%, and 37.4%, respectively; implantation: 14.6%, 19.9%, and 19.8%, respectively). CONCLUSION(S): The double (consecutive) transfer of early embryos and blastocyst(s) does not offer any advantage over the traditional early transfer. This may be from the adverse effect of the second transfer on the implantation process.

Outcome of pregnancies derived from assisted reproductive technologies: IVF versus ICSI.

PURPOSE: To compare the course and outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies. METHODS: A retrospective study was conducted in a university-affiliated IVF unit with 200 patients who conceived in 1996-1997, 100 with ICSI and 100 with IVF. Data were retrieved from our prospectively created computerized database. In addition, all patients were interviewed by telephone, and the interviewing physician completed a detailed questionnaire. Findings for the IVF and ICSI pregnancies were compared. The main outcome measures were maternal age, implantation rate, early pregnancy complications, clinical abortion rate, multiple pregnancy delivery rate, gestational age at delivery, mode of delivery, and birth weight. RESULTS: In all, 238 children were born, including 104 singleton infants (45 IVF, 59 ICSI), 49 twin pairs (28 IVF, 21 ICSI), and 12 triplet sets (3 IVF, 9 ICSI). Statistically significant differences between the ICSI and IVF groups were noted for maternal age (31.3 +/- 4.4 vs. 33.4 +/- 4.8, respectively, P < 0.005) and clinical abortion rate (11% vs. 24%, respectively, P < 0.05). CONCLUSIONS: ICSI pregnancies in our series were characterized by a lower clinical abortion rate than IVF pregnancies, probably because of the mean younger age of the ICSI group.

Follicle-stimulating hormone treatment for men with idiopathic oligoteratoasthenozoospermia before in vitro fertilization: the impact on sperm microstructure and fertilization potential.

OBJECTIVE: To assess the effect of FSH on sperm fertilization potential and sperm intracellular structure in men with oligoteratoasthenozoospermia and a proven low fertilization rate in IVF. DESIGN: Prospective, randomized, partial crossover study. SETTING: IVF Unit, Golda Campus, Rabin Medical Center, Petah Tikva, Israel. PATIENT(S): Forty normogonadotropic, normogonadal men with oligoteratoasthenozoospermia and at least one previous IVF attempt in which fertilization failed or the fertilization rate was <30%. INTERVENTION(S): The men were randomly assigned to treatment with daily injections of 75 IU of FSH or 150 IU of FSH for at least 60 days before IVF treatment. A control group of men underwent an IVF cycle without treatment and then were randomly assigned tojoin group 1A or 1B for an additional IVF cycle with treatment. MAIN OUTCOME MEASURE(S): LH, FSH, and testosterone levels during FSH treatment, evaluation of ultramorphologic changes in sperm by electron microscopy, and comparison of fertilization rates in the control and study groups. RESULT(S): After treatment with 75 IU or 150 IU of FSH, the mean fertilization rates were 19.7% and 20.5%, respectively, compared with a 5.8% fertilization rate in the study control cycles. CONCLUSION(S): Prolonged treatment with FSH results in a significant increase in fertilization rates. This effect may be related to improvements in subcellular components of the sperm.

The rationale for requesting a second consecutive sperm ejaculate for assisted reproductive technology.

We assessed the value of requesting a second semen sample provided within 1 hour of the first in cases of unacceptable ejaculate quality (compared to previous occasions) or very poor semen characteristics. The study population consisted of 109 males with severe oligo-terato-astenospermic (OTA) syndrome in an assisted reproduction program. Semen volume, sperm count and sperm motility were recorded in the first and second samples with a Makler Counting Chamber before sperm processing, and total motile sperm in the ejaculate was calculated. Differences in sperm parameters between the consecutive samples were determined by paired-sample t test. In 36 cases (33%) the second sample was found to be superior in quality to the first and was therefore used for the fertilization process. Of the 12/109 cases in which the first ejaculate demonstrated no motile sperm, five (41%) had detectable motile sperm in the second (total 0.1 x 10(6), 0.2 x 10(6), 0.3 x 10(6), 8.4 x 10(6) and 20.8 x 10(6)). We conclude that a request for second ejaculate immediately after the first in males with poor semen quality or no detectable motile sperm can yield a better sample in a significant percentage of cases. Using this method, clinicians can avoid the utilization of elaborate sperm processing techniques and the need for unnecessary micromanipulative fertilization.

The role of purified follicle stimulating hormone therapy in the male partner before intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the impact of long-term purified FSH (pFSH) therapy in male partners before intracytoplasmic sperm injection (ICSI). DESIGN: Prospective, randomized, controlled study. SETTING: Large university-based IVF unit. PATIENT(S): Seventy-eight patients made up the study and control groups (39 patients each). All patients had severe male factor infertility. INTERVENTION(S): Induction of ovulation, oocyte retrieval, ICSI, and ET were carried out in both groups. In the study group, male partners received pFSH (75 IU FSH, <1 IU LH) for > or = 50 days before oocyte retrieval. MAIN OUTCOME MEASURE(S): Fertilization rate, embryo quality, implantation and pregnancy rates. RESULT(S): Fertilization and pregnancy rates were higher in the study group (68% and 35.9%, respectively) were higher than in the control group (59% and 17.9%, respectively), although the differences did not reach statistical significance. The implantation rate was significantly higher in the study group (15.5% versus 6.5%). The study group showed a trend toward a higher number of better-quality embryos per transfer (mean +/- SD, 2.2 +/- 1.6 versus 1.6 +/- 1.6). CONCLUSION(S): Purified FSH therapy in male partners before ICSI improves implantation rate. Improved embryo quality may be a contributory factor.

Standard in vitro fertilization or intracytoplasmic sperm injection in advanced female age--what may be expected?

This study was conducted to evaluate the current results of standard in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the elderly (> or = 40 years of age) female population. Oocyte recovery, fertilization, embryo transfer, pregnancy and cumulative pregnancy rates were assessed. The results were analyzed for: the entire elderly population; the standard IVF group (group 1); all those in the ICSI group (group 2); and ICSI for severe male-factor category (group 3). A total of 330 IVF and 158 ICSI treatment cycles were carried out in 249 women. Forty-five (9.2%) clinical pregnancies were achieved. This rate was not statistically different from those achieved for groups 1, 2 and 3 (9.1%, 9.5% and 6.8%, respectively). The cumulative pregnancy rate for a total of five cycles was 19.2% and 26.4% for groups 1 and 2, respectively. For those who started their treatments at > or = 40 years, the cumulative pregnancy rate for three cycles was 26.5% and 36.5% in groups 1 and 2, respectively. These results clearly demonstrate that female age is a major success determinant, with similar influence on both standard IVF and ICSI therapy modalities.

Fibrin glue improves pregnancy rates in women of advanced reproductive age and in patients in whom in vitro fertilization attempts repeatedly fail.

OBJECTIVE: To evaluate the possible contribution of fibrin sealant to the ET stage of IVF. DESIGN: Case-control study. SETTING: An assisted reproductive technology unit that performed 2,535 treatment cycles from 1996-1997. PATIENT(S): All consecutively seen patients who underwent ET from January 1996 to September 1997. INTERVENTION(S): All women who underwent ET with the aid of fibrin sealant during the study period were compared with those who underwent standard ET (controls). Thereafter, a case-control study was conducted on the first consecutively seen 174 women who underwent ET with fibrin sealant and a control group that was matched for age and number of previous unsuccessful cycles. MAIN OUTCOME MEASURE(S): Patient age, number of previous unsuccessful IVF attempts, number of embryos transferred, and pregnancy rates. RESULT(S): During the study period, ET was performed with fibrin sealant in 265 women and by the standard procedure in 1,402 women. Women in the fibrin sealant group were significantly older. The pregnancy rate was not significantly different between the groups in the whole-cohort study (20.4% versus 23.1%), but it was significantly higher in the fibrin sealant group in the case-control study (25.3% versus 14.9%). This also was true when the older women (>35 years) and the women with > or =4 previous failed IVF attempts were analyzed separately (23.2% versus 9.8% and 26.1% versus 13.4%, respectively). CONCLUSION(S): The use of fibrin sealant in ET appears to be beneficial in women of advanced reproductive age and in patients in whom IVF attempts repeatedly fail.

Pharmacokinetics of natural progesterone administered in the form of a vaginal tablet.

Our study was conducted to assess the pharmacokinetics of natural progesterone administered in the novel formula of an effervescent vaginal tablet. Fifty post-menopausal women, with a median age of 43.5 years (range 28-55), volunteered to participate in the research. All women discontinued their hormonal replacement therapy 1 month prior to the study. The pharmacokinetics of 50 and 100 mg of progesterone administered as a vaginal tablet were evaluated. After the initial administration of 50 mg or 100 mg, a mean serum Cmax of 20.43 +/- 8.01 nmol/l and 31.61 +/- 12.62 nmol/l (P < 0.0004) was reached at a Tmax of 6.1 +/- 2.63 and 6.4 +/- 3.35 h respectively. The terminal half-life was 13.18 +/- 1.3 and 13.7 +/- 1.05 h respectively. Continuous use of the 100-mg tablet resulted in a mean serum progesterone concentration of 26.08 +/- 13.96 nmol/l and 21.42 +/- 16.32 nmol/l after 14 and 30 days respectively. Women >40 years were found to have a significantly lower Tmax compared to younger women (P = 0.02). The continuous use of vaginal progesterone did not influence the hormonal, liver or lipid profiles evaluated. Only three (6%) women suffered from mild vaginal irritation. Natural progesterone given as a vaginal tablet is well tolerated, safe and an easily administered treatment. Even in a non-oestrogenized vagina the absorption was efficient and the 100 mg dosage resulted in adequate serum progesterone concentrations.

Does female age affect embryo morphology?

Deteriorating oocyte quality is commonly believed to be the primary determinant of the decreased implantation potential in older women. We assessed the influence of age on embryo morphology in standard in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) modalities. All 6350 consecutive embryos (2990 IVF, 3360 ICSI) obtained in our Assisted Reproductive Technology Unit from January 1996 through June 1997 were included. High quality embryos were defined as those with equal-sized blastomeres and < 10% fragmentations and a cleavage rate of four cells on day 2 or eight cells on day 3 transfers. The results were analyzed for the standard IVF group, the ICSI group, and the ICSI subgroup with severe male factor infertility (< or = 1 x 10(6) total motile spermatozoa in the ejaculate). For standard IVF, a positive association was observed between female age and increased proportion of good quality embryos. No such association was detected for the ICSI cycles (whole group or subgroup). We conclude that in standard IVF, embryo quality, as reflected by embryo morphology, does not deteriorate with increased maternal age.

Morphology and clinical outcomes of embryos after in vitro fertilization are superior to those after intracytoplasmic sperm injection.

OBJECTIVE: To compare embryos obtained after IVF and intracytoplasmic sperm injection (ICSI) regarding morphology and the likelihood of achieving clinical pregnancy. DESIGN: Case-control study. SETTING: An IVF unit controlling 1,310 cycles in 1996. PATIENT(S): Women having a total of 477 IVF and 475 ICSI consecutive cycles. INTERVENTION(S): Ovarian stimulation, IVF-ET, or ICSI-ET for all couples. MAIN OUTCOME MEASURE(S): Number of grade-A embryos transferred, preclinical pregnancy losses, and clinical pregnancy rates in IVF and ICSI cycles. RESULT(S): In comparison with the ICSI group, the IVF group showed significantly more grade-A embryos available for transfer (mean, 2 +/- 1.6 versus 1.8 +/- 1.5), significantly fewer preclinical pregnancy losses (1.6% versus 4%), and significantly higher clinical pregnancy rates (25% versus 19.1%). CONCLUSION(S): Embryos obtained after IVF are superior to those obtained after ICSI in relation to embryo morphology and the likelihood of achieving clinical pregnancy.