Evaluation of cycle-to-cycle variation of endometrial responsiveness using transvaginal sonography in women undergoing assisted reproduction.

OBJECTIVES: To investigate the variation of endometrial responsiveness between cycles within the same women undergoing assisted reproduction. METHODS: The sonographic endometrial thickness in ovarian stimulation cycles was compared with that of subsequent natural cycles. One hundred and thirty-six ovarian stimulation cycles of in-vitro fertilization and embryo transfer were evaluated. Women who did not conceive in in-vitro fertilization cycles were subsequently seen in natural cycles (n = 97) or the next in-vitro fertilization cycle (n = 39). Based on a receiver-operating characteristics (ROC) curve using endometrial thickness to predict pregnancy, the first in-vitro fertilization cycles were classified according to the endometrial thickness as optimal (> 8 mm) in 98 cycles, or suboptimal (< or = 8 mm) in 29 cycles. Similarly, spontaneous cycles were classified as suboptimal (< or = 7 mm) in 28 cycles and optimal (> 7 mm) in 69 cycles. RESULTS: The pregnancy rates were significantly lower (P < 0.05; Fisher's Exact test) in the suboptimal group in both the in-vitro fertilization and frozen embryo transfer cycles. There was a strong correlation (r2 = 0.745) and a significant difference (P < 0.001; Wilcoxon signed rank sum test) between the endometrial thickness of stimulation and natural cycles. CONCLUSION: It is possible to predict the occurrence of optimal or suboptimal endometrial response in natural cycles of women, after evaluation in stimulated cycles, with a high degree of reliability. Risk of implantation failure can be identified before subsequent treatment cycles and adjuvant therapeutic strategies may be planned to improve the endometrial response before embryo transfer.

Ultrasound-guided embryo transfer: a prospective randomized controlled trial.

BACKGROUND: Recent reports suggested that ultrasound guidance during embryo transfer might improve the pregnancy rate. METHODS: A prospective randomized controlled trial was performed to compare embryo transfer under ultrasound guidance versus the clinical touch method. A total of 800 embryo transfers was studied; 400 were randomized to ultrasound-guided transfers and 400 were randomized to the clinical touch group. Of these, 441 were fresh cycles and 359 were frozen-thawed cycles. RESULTS: The clinical pregnancy rate was 26.0% in the ultrasound-guided group and 22.5% in the clinical touch group; the difference was not statistically significant. The ongoing pregnancy rate was 23.5% in the ultrasound-guided group compared with 19.0% in the clinical touch group and the difference was again not statistically significant. The implantation rate was slightly higher in the ultrasound-guided group (15.3%) than the clinical touch group (12.0%) (P = 0.048). There were no differences in the incidences of ectopic pregnancy, miscarriage and multiple pregnancy between the two groups. CONCLUSIONS: A significant improvement in implantation rate was observed following the use of ultrasound guidance during embryo transfer. The extent of improvement in the pregnancy rate may depend on the specific techniques and methods of embryo transfer used in individual centres.

Deletions within the azoospermia factor subregions of the Y chromosome in Hong Kong Chinese men with severe male-factor infertility: controlled clinical study.

OBJECTIVE: To determine the patterns and the prevalence of microdeletions in the azoospermia factor subregions of the Y chromosome in Hong Kong Chinese men with severe male-factor infertility. DESIGN: Controlled clinical study. SETTING: Reproductive centre of a university teaching hospital, Hong Kong. PARTICIPANTS: Fifty-eight men with severe male-factor infertility who participated in the in vitro fertilisation programme from May 1998 through March 1999, and 46 male volunteers with proven fertility. MAIN OUTCOME MEASURES: Polymerase chain reaction analysis of DNA from peripheral blood lymphocytes using six loci spanning the AZFa, AZFb, and AZFc subregions of the Y chromosome. RESULTS. No microdeletions were detected in the fertile controls or in patients with obstructive azoospermia. Deletions within the AZFc subregion were found in 9% (4/44) of men with non-obstructive azoospermia or severe oligospermia. Neither AZFa nor AZFb deletions were detected in any participants. CONCLUSION: Deletions within the azoospermia factor subregions of the Y chromosome are associated with severe male-factor infertility in Hong Kong Chinese men.

The effect of ageing on female fertility in an assisted reproduction programme in Hong Kong: retrospective study.

OBJECTIVE: To analyse the effect of ageing on female fertility in an in vitro fertilisation programme in Hong Kong. DESIGN: Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS: Seven hundred and seventy-one women in whom 1336 cycles of in vitro fertilisation were initiated between 1 January 1986 and 31 December 1995. MAIN OUTCOME MEASURES: Patient age and indications for treatment; hormonal response; and the number of cancelled cycles, oocytes retrieved, oocytes fertilised, cleaving embryos, embryos transferred, and clinical pregnancies. RESULTS: Compared with women aged or =36 years (n=398) had a significantly higher cycle cancellation rate (19.3% versus 10.4%), fewer oocytes retrieved per retrieval cycle (6.6 versus 9.0), fewer oocytes fertilised per retrieval cycle (5.0 versus 7.0), fewer cleaving embryos per retrieval cycle (4.8 versus 6.8), and lower serum oestradiol level (9735 [standard deviation, 5681] pmol/L versus 10 708 [5916] pmol/L) despite a larger amount of human menopausal gonadotrophin having been used (all variables, P<0.01; Chi squared test). The clinical pregnancy rate per initiated cycle (range, 7.5%-13.0%) decreased with advancing age (P<0.01; Chi squared test). CONCLUSION: Ageing has a significant deleterious effect on women's reproductive capability. Women should be encouraged to seek early medical advice and treatment for subfertility.

High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles.

High oestradiol concentrations may be detrimental to the success of in-vitro fertilization (IVF) treatment. A total of 1122 women aged <40 years who were undergoing their first IVF cycle were evaluated retrospectively. Serum oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration were categorized into three groups: group A <10 000 pmol/l; group B 10 000-20 000 pmol/l and group C >20 000 pmol/l. In fresh cycles, group A had significantly lower pregnancy rates per transfer (16.2 versus 23.7% respectively, P = 0.005, chi(2)) and implantation rates (8.7 versus 11.7% respectively, P = 0.037, chi(2)), when compared with group B. The pregnancy rate per transfer in group C was significantly lower than that in group B (12.1 versus 23.7%, P = 0.049, chi(2)) and group C had the lowest implantation rate (6.4%). In frozen-thawed embryo transfer cycles, implantation rates in groups A, B and C were similar (7.5, 8.1 and 9.6% respectively) and the pregnancy rates were also comparable in all groups. In conclusion, high serum oestradiol concentrations in fresh IVF cycles may adversely affect implantation and pregnancy rates. Embryo quality seemed unaffected as excess embryos from different groups had similar implantation and pregnancy rates in frozen-thawed embryo transfer cycles. The reduced implantation was probably due to an adverse endometrial environment resulting from high serum oestradiol concentrations.

Maternal serum alpha-fetoprotein and human chorionic gonadotrophin in pregnancies conceived after intracytoplasmic sperm injection and conventional in-vitro fertilization.

Data in the Caucasian population suggest that maternal serum alpha-fetoprotein (AFP) and unconjugated oestriol concentrations are reduced and human chorionic gonadotrophin (HCG) concentrations are elevated in pregnancies conceived after in-vitro fertilization (IVF), leading to a higher than expected Down's syndrome screen-positive rate. There are no previous reports on the serum marker values in pregnancies conceived after intracytoplasmic injection (ICSI). Between 1996 and 1998, we measured maternal serum total HCG and AFP concentrations between 15 and 20 weeks gestation in 42 in-vitro fertilization (IVF) pregnancies and 23 ICSI pregnancies with known normal outcome. The results were compared with that of 2799 naturally occurring singleton pregnancies who were known to have a normal outcome. Median AFP multiple of the median (MOM) in ICSI pregnancies was significantly reduced to 0.76 compared with both that of the controls and that of the IVF pregnancies. For the IVF pregnancies, median HCG MOM was elevated to 1.15, and median AFP MOM was reduced to 0.88 compared with the controls, but these differences were not statistically significant. In both the IVF and ICSI pregnancies the changes might result in a falsely high Down's syndrome risk. In particular, the reduced AFP concentration in ICSI pregnancies was substantial. If this preliminary finding is substantiated by other series, the appropriate adjustment needs to be made to allow for valid interpretation of the screen result and to avoid an unnecessarily high false positive rate.

A prospective randomized control study to compare the effect of serum and a commercial serum substitute (Plasmanate) on the outcome of assisted reproduction program.

OBJECTIVES: To compare the effect of supplementation of serum and Plasmanate, a commercial serum substitute, to culture medium on the IVF outcome. METHODS: One hundred eighty-nine subfertile couples were prospective randomized into the serum and the Plasmanate group during their IVF treatment. In vitro experiment was also performed to determine the fraction of Plasmanate that might affect embryo development. RESULTS: The pregnancy rate were similar in both groups. The fertilization rate, the number of gestational sacs and good quality spare embryos suitable for cryopreservation were higher in the serum group than the Plasmanate group. However, these differences did not reach statistical significance. Significantly more embryos in the former cleaved to more than 4 cells at the time of transfer than the latter (p < 0.05). Ultrafiltration study showed that this inhibitory effect resided in the low molecular weight fraction (< 30-KD) of Plasmanate. CONCLUSION: Serum is slightly better than Plasmanate as a protein supplement. However, Plasmanate may still be used for short term embryo culture in assisted reproduction.

An analysis of ectopic pregnancies following in vitro fertilisation treatment in a 10-year period.

Of clinical pregnancies in our in vitro fertilisation (IVF) programme, 5.4% were ectopic and 0.85% of clinical pregnancies (15% of ectopic pregnancies) were heterotopic. Ectopic pregnancies were more common after IVF/embryotransfer (ET) than frozen embryotransfer (FET). Although there was a suggestion that tubal factors were more common in those with ectopic pregnancies, the difference did not reach statistical significance. No relationship existed with regard to the ovarian stimulation regimen, the dosage/ duration of human menopausal gonadotrophin used, the details of embryo transfer and number of embryos transferred. Patients who develop ectopic pregnancies after IVF can be counselled that they have a good chance of achieving a normal pregnancy with subsequent attempts.

The value of a single sensitive urine pregnancy test in prediction of pregnancy outcome.

A simple and reliable indicator for pregnancy outcome will be valuable clinically for patient management and for counselling women whose pregnancies are results of subfertility treatment. This study aimed at evaluating the ICON II test, a simple semiquantitative sensitive urine pregnancy test, in predicting pregnancy outcome in women who conceived after various forms of subfertility treatment. The ICON II test was performed on day 20 after the ovulating dose of hCG administration or spontaneous LH surge. One hundred and forty-five consecutive pregnancies were studied, 99 being viable and 46 nonviable which included subclinical abortion, clinical abortion and ectopic pregnancies. There was a significant difference in the luteal serum progesterone and hCG levels between viable and nonviable pregnancies. There was also a significant difference in the ICON II test result, i.e. either weakly positive (hCG of 25-50 IU/l) and positive (hCG > 50 IU/l) and the pregnancy outcome (p < 0.0001). The specificity of a weakly positive ICON II test in predicting poor pregnancy outcome was 98.8% whereas the sensitivity was 28.6%. In conclusion, a weakly positive ICON II test is useful in predicting poor pregnancy outcome.

Factors affecting the incidence of polyploidy in a human in vitro fertilization program.

OBJECTIVE: To study the factors affecting the incidence of polyploidy in an assisted reproduction program. DESIGN: Retrospective analysis. SETTING: University-based subfertility clinic. PATIENTS AND METHODS: Subfertile patients were treated in 163 treatment cycles of in vitro fertilization (IVF) or pronuclear stage tubal transfer (PROST). The relationship between the incidence of polyspermy and the indication of subfertility, the stimulation protocol, the oocyte, and the semen parameters were analyzed. RESULTS: Eighty-nine of the 1,149 oocytes were polyploid (7.8%). The incidence of polyploidy was not affected by the indication for IVF, the age of the patients, the stimulation protocol, the maturity of oocytes as assessed by the appearance of the cumulus, the sperm concentration, the number of sperm inseminated, the serum estradiol level, and the number of oocytes retrieved. The incidence was increased when: (1) the serum estradiol fell before the administration of human chorionic gonadotrophin; (2) the oocyte retrieval-insemination interval was 6 hours or more; (3) the sperm motility was 70% or more; (4) the percentage of sperm with normal morphology was 50% or more. CONCLUSION: The incidence of polyploidy was affected by the serum estradiol pattern, the preinsemination interval, sperm motility, and percentage of morphologically normal sperm.

The value of transabdominal pelvic ultrasonography in monitoring of ovulation induction with gonadotropins.

Seventy-five patients with a total of 306 human menopausal gonadotropin treatment cycles over the period 1984-1989 were analysed retrospectively to evaluate the value of transabdominal pelvic ultrasonography in prevention of complications arising from ovulation induction with human menopausal gonadotropins. There were 60 pregnancies giving a pregnancy rate of 19.6% per cycle. There was positive correlation between the number of follicles > or = 14 mm in mean diameter and the incidence and degree of hyperstimulation (p < 0.005) as well as the incidence of multiple pregnancies (p < 0.01). Ultrasonography is a useful adjunct for monitoring in such a program.

Efficacy of the urinary hemagglutination test (Higonavis) and enzyme immunoassay (Ovustick) in detection of the spontaneous luteinizing hormone surge in an in vitro fertilization/gamete intrafallopian transfer (IVF/GIFT) program.

Fifty-eight treatment cycles in an in vitro fertilization/gamete intrafallopian transfer (IVF/GIFT) program were studied to compare the efficacy of two urinary methods, hemagglutination test (Higonavis) and enzyme immunoassay (Ovustick), in detection of spontaneous luteinizing hormone (LH) surge. If an isolated rise in urinary LH level was taken as indicative of LH surge, the false-positive rate was 36.7% for Higonavis and 10.2% for Ovustick. The difference was statistically significant (P less than 0.001). If only a sustained rise in urinary LH was taken to indicate LH surge, the false-positive rate was 6.1% for Higonavis and 0% for Ovustick. In the seven cycles with a spontaneous plasma LH surge, there was a positive correlation between the plasma LH levels and the two urinary assay methods in six cycles (85.7%). Compared to plasma LH, there was a mean delay of 17.4 hr by the Higonavis test and 15.6 hr by the Ovustick test. If a sustained rise in urinary LH levels was taken as indicative of LH surge, both methods are quite accurate but the Ovustick appeared to be more specific.

Predictive value of sperm morphology and movement characteristics in the outcome of in vitro fertilization of human oocytes.

One hundred fourteen semen samples from Chinese males were analyzed for routine semen parameters including the semen volume, sperm count, percentage motility, and percentage normal morphology. Of these 114 samples, 54 also had movement characteristics of seminal and swim-up sperm evaluated by the computer image analyzer system (Cellsoft; Cryo Resources Co., New York). All semen samples were subjected to the swim-up procedure to harvest the motile sperm before inseminations of human oocytes. Fertilization was considered to have occurred when at least one oocyte was observed with two or more pronuclei. Semen samples were classified as infertile (0% fertilization rate; N = 32) or fertile (greater than 0% fertilization rate; N = 82) before statistical analyses. There was a significant difference (P less than 0.005) in percentage normal morphology of seminal sperm between the fertile (mean +/- SE; 67.3 +/- 1.2%) and the infertile (59.3 +/- 2.2%) samples. The percentage normal morphology of seminal sperm correlated (r = 0.3049; P less than 0.002) with the fertilization rate and this parameter was selected by the multivariate stepwise discriminant analysis as the discriminator capable of predicting the fertilization rate with 57.9% accuracy. Statistical analyses of samples where sperm movement was also evaluated demonstrated that there was significant differences (P less than 0.01) between the fertile (N = 38) and the infertile (N = 16) samples in percentage normal morphology of seminal sperm (67.8 +/- 1.8% vs 56.2 +/- 2.6%) and curvilinear velocity of swim-up sperm (89.2 +/- 3.5 vs 68.2 +/- 7.2 microns/sec).(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic value of sperm function tests and routine semen analyses in fertile and infertile men.

The results of routine semen analyses, the zona-free hamster oocyte penetration test, the hypoosmotic swelling test, and semen adenosine triphosphate levels were studied in 66 fertile and 130 infertile men. Multivariate discriminant analysis demonstrated that routine semen parameters including semen volume, sperm count, percent sperm motility, and percent normal spermatozoa in combination could predict the fertility of these patients with 70.4% accuracy. Of the three sperm function tests evaluated, the zona-free hamster oocyte penetration test and the hypoosmotic swelling test were selected by the multivariate discriminant analysis as variables capable of providing significant information on the fertility status of the patients. However, the addition of the results of these two tests to the routine semen analysis did not significantly improve the predictability of fertility. The overall correct prediction rate was 77.6% after incorporation of the results of these two sperm function tests. In this group of subjects, the presently available sperm function tests did not predict the fertility status of a patient with a high degree of accuracy.

Multivariate discriminant analysis of the relationship between the hypo-osmotic swelling test and the in-vitro fertilizing capacity of human sperm.

Multivariate discriminant analysis was used to evaluate the usefulness of routine semen parameters and the hypo-osmotic swelling test (HOST) as predictors of the in-vitro fertilizing capacity of human sperm as assessed by the zona-free hamster egg penetration assay (HEPA). Eighty-eight semen samples from untreated patients attending an infertility clinic were analysed. Semen samples were classified into the following three groups before statistical analysis: group 1--positive sperm penetration (greater than or equal to 10%, n = 39); group 2--borderline penetration rates for HEPA (greater than 0% but less than 10%, n = 39) and group 3--negative sperm penetration (0%, n = 10). The percentage of sperm with normal morphology and sperm count were found to be significant in discriminating between semen samples exhibiting different in-vitro fertilizing capacity. These two discriminating variables in combination gave an overall correct classification rate of 45.5%. The multivariate discriminant analysis was also performed after excluding the data of group 2 semen samples (n = 39), which exhibited borderline sperm penetration rates. As a result, three discriminating variables including semen volume, sperm count and the percentage of sperm with normal morphology were selected. These three variables in combination could accurately predict whether a semen sample would exhibit positive sperm penetration (group 1) or negative sperm penetration (group 3) with an overall accuracy of 75.5%. The percentage of swollen sperm after hypo-osmotic treatment was not related to the HEPA result, as determined by linear correlation and multiple regression analyses, and did not give additional information about the in-vitro fertilizing capacity of sperm as evaluated by multivariate discriminant analysis.

Chronic sinopulmonary disease in Chinese patients with obstructive azoospermia.

The prevalence of chronic infections of the nasal sinuses and the lung (chronic sinopulmonary disease) was investigated in 33 Chinese patients with obstructive azoospermia who were compared with 32 patients with azoospermia due to failure of the germinal epithelium. Ten out of the group of 33 patients with obstructive azoospermia had congenital absence of the vas and/or epididymis and were excluded from that group. The patients with obstructive azoospermia had normal testis size, normal levels of serum FSH and LH, lower seminal fluid fructose, and a higher incidence of serum sperm agglutinating and immobilizing antibodies when compared with the group with damage to the germinal epithelium. The number of patients with symptoms of chronic sinopulmonary infections were similar in all groups. One patient with obstructive azoospermia had bronchiectasis. All other patients had normal chest x-ray studies. About 40% of the patients in all three groups had abnormal sinus X-rays. However, the nonsmoking patients with obstructive azoospermia had a statistically significant (P less than 0.05) lower mid-expiratory flow rate than the nonsmoking patients with nonobstructive azoospermia. Only three additional patients with obstructive azoospermia had both abnormal sinus x-ray and a reduced mid-expiratory flow rate, suggestive of Young's syndrome. It was concluded that Young's syndrome (sinopulmonary infections associated with acquired obstructive azoospermia) is much less common in Chinese men (four out of 23, 17%) and their sinopulmonary problems are less severe than in Caucasians.

Homozygous alpha-thalassaemia: clinical presentation, diagnosis and management. A review of 46 cases.

Forty-six hydropic infants with homozygous alpha-thalassaemia born during a period of 10 years have been reviewed. The incidence was 1:1550 total births, and accounted for 81% of all non-immune hydrops. The male to female ratio was 1:1.4. There was increased incidence of anaemia, pregnancy induced hypertension, antepartum haemorrhage, malpresentation, prematurity, fetal distress, difficult vaginal delivery, caesarean section, retained placenta, postpartum haemorrhage and congenital abnormalities. Antenatal diagnosis by DNA hybridization with subsequent abortion of the affected fetuses is the best method to decrease maternal morbidity and to reduce the incidence of hydrops fetalis in couples at risk. For those with no previous history, but with early onset hypertension and/or polyhydramnios, sonography is useful in making an earlier diagnosis, and in reducing avoidable morbidity, because DNA analysis can be done before caesarean section and aggressive neonatal management is instituted.