Transport in vitro fertilization--a novel scheme for community-based treatment.

OBJECTIVE: To provide an inexpensive and extensive in vitro fertilization (IVF) service for the Mersey Region, United Kingdom. DESIGN: Twenty-four transport IVF patients treated in two district general hospitals using the central university laboratory as co-ordination point for treatment schedule and embryology. Outcomes were compared with 26 control patients treated in the central unit. SETTING: Royal Liverpool University Hospital, a central IVF unit, and two district general hospitals in the Mersey Region. PATIENTS: Fifty patients under 35 years of age with irreversible tubal damage selected and treated by IVF, half in the central unit and the other half in two district general hospitals. MAIN OUTCOME MEASURES: Pregnancy rate (PR) in the different centers. RESULTS: A PR of 42.3% per cycle in the peripheral hospitals compared with 30.7% per cycle in the central unit. CONCLUSION: Transport IVF is an inexpensive and feasible alternative to standard IVF in a central unit for patients without access to central units.

The sperm deformity index: a reliable predictor of the outcome of oocyte fertilization in vitro.

OBJECTIVE: To evaluate a novel expression of sperm morphological parameters, the sperm deformity index, as a predictor of fertilization in vitro. DESIGN: Prospective blind clinical trial. SETTING: Academic tertiary referral center. INTERVENTION(S): Detailed sperm morphological assessment applying strict morphological criteria and a multiple entry technique for an unselected male population undergoing IVF. The sperm deformity index, defined as the average number of deformities per sperm assessed, was calculated. PATIENT(S): One hundred fifty-eight patients undergoing IVF treatment. Females with conditions negatively influencing fertilization were excluded. MAIN OUTCOME MEASURE(S): Fertilization rates and pregnancy. RESULT(S): Seventy-three percent of patients achieved fertilization. Patients achieving fertilization had a significantly higher median proportion of normal forms and a significantly lower median sperm deformity index than the nonfertilizers. The receiver operator characteristic (ROC) curves identified cutoff points that maximized the sum of sensitivity and specificity at sperm deformity index 1.6 and normal forms 4%. The sperm deformity index had a greater sensitivity (96%), specificity (72%), positive predictive value (90%), and negative predictive value (86%) than the proportion of normal sperm morphology (87%, 69%, 89%, 66%, respectively) at the optimal cutoff points. The area under the ROC curve was greater for the sperm deformity index (0.875) than for the proportion of normal sperm morphology (0.622). Achieving pregnancy did not correlated with sperm morphology. CONCLUSION(S): The sperm deformity index is a more reliable predictor of the outcome of fertilization in vitro than the proportion of normal sperm morphology and can assist to identify patients who require techniques such as intracytoplasmic sperm injection.

Human sperm head morphometric distribution and its influence on human fertility.

OBJECTIVE: To study the distribution of live sperm head size in semen and sperm preparations as a predictor of fertility. DESIGN: Prospective blind clinical trial. SETTING: Academic tertiary referral center. PATIENT(S): One hundred fifty-five patients undergoing IVF treatment. Females with conditions negatively influencing fertilization were excluded. INTERVENTION(S): Morphometric analysis (head area, major axis, minor axis, and elongation ratio) of video images of sperm in semen and swim-up preparations used for IVF treatment was performed with a Hamilton-Thorne analyzer V 8.1 (Hamilton-Thorn Research, Beverly, MA). MAIN OUTCOME MEASURE(S): Oocyte fertilization. RESULT(S): Seventy-four percent of patients achieved fertilization. Fertilizers and nonfertilizers had different sperm head area distribution. The fertilizers had a significantly smaller interquartile range of sperm head area and of major axis in both semen and sperm preparation compared with the nonfertilizers. A subgroup of men who had fathered a child naturally had a more uniform sperm head area in semen with a significantly smaller median compared with those who failed to father a child naturally with their healthy female partner. We used multiple logistic regression applying forward stepwise selection of variables in building three predictive models of probability of fertilization. CONCLUSION(S): Successful IVF or history of fathering a child was associated with a more uniform sperm head area in semen and sperm preparation.

Evaluation of different sperm function tests as screening methods for male fertilization potential--the value of the sperm migration test.

OBJECTIVE: To assess the value of different sperm function screening tests in predicting fertilization. DESIGN: Prospective study. SETTING: Academic tertiary referral center for fertility treatment. PATIENTS: Ninety-five couples attending for initial screening and IVF-ET. Only cycles where three or more grade I oocytes were collected were included, and patients with endometriosis were excluded. INTERVENTIONS: Each patient had a standard semen analysis, cervical mucus (CM) penetration test, hypo-osmotic swelling test, and sperm migration test performed between 4 and 8 weeks before IVF-ET. MAIN OUTCOME MEASURES: The correlation between sperm function test results and the percentage of fertilized oocytes and the power of the tests to predict fertilization. RESULTS: The sperm migration test correlated highly with fertilization rate (r = 0.62) and was most useful in identifying the group of patients likely to achieve fertilization (Odds ratio [OR] 0.07, confidence interval [CI] 0.02 to 0.2). The CM penetration test showed a moderate correlation with fertilization rate (r = 0.45) and some predictive power (OR 0.37, CI 0.13 to 1.00). Sperm concentration, but not motility or normal morphology, showed slight correlation with fertilization rate (r = 0.28) but the combination of normal semen parameters did not distinguish patients likely to achieve fertilization (OR 1.51, CI 0.62 to 3.65). The hypo-osmotic swelling test did not correlate with fertilization rate (r = 0.21). CONCLUSIONS: This study evaluated the predictive power of several simple tests available for use in most laboratories as screening tests of sperm fertilization potential. Apart from sperm concentration, normal traditional semen characteristics were of little clinical benefit. The hypo-osmotic swelling test had no predictive power. The CM penetration test correlated with fertilization rate but might be difficult to perform routinely as a continuous supply of suitable CM would be required. The sperm migration test proved to be the best discriminator of sperm fertilization potential and should be considered as a first level screening test in the assessment of male fertility.

Role of mitotic control in spermatogenesis.

OBJECTIVE: To study the correlation between the incidence of sex chromosome aneuploidies in the somatic cells and spermatozoa in karyotypically normal infertile men and fertile donors. DESIGN: A prospective, phase two, controlled study. SETTING: A teaching Hospital Reproductive Medicine and Medical Genetics Units. PATIENT(S): Ten patients with idiopathic oligozoospermia and 10 sperm donors with proven fertility, all with a normal karyotype 46, XY. INTERVENTION(S): Multicolor fluorescence in situ hybridization (FISH) of peripheral blood lymphocytes and spermatozoa using a probe cocktail containing the alpha satellite DXZ1 for the X centromere, DYZ1 for the heterochromatic region of the long arm of the Y, and cosmids D21S259, D21S341, and D21S342 for Down syndrome critical region of chromosome 21. MAIN OUTCOME MEASURE(S): The incidence of chromosome X, Y, and 21 aneuploidies in peripheral lymphocytes and spermatozoa in both groups. RESULT(S): The incidence of aneuploidies related to chromosomes X, Y, and 21 were significantly higher in peripheral lymphocytes and spermatozoa of infertile men compared with donors. There was a positive correlation between the incidence of chromosome aneuploidies in the somatic cells and sperm in all men. CONCLUSION(S): These findings provide suggestive evidence for the importance of mitosis in spermatogenesis and the role of mitotic instability in unexplained oligozoospermia.

The hypo-osmotic swelling test in recurrent miscarriage.

OBJECTIVE: To determine whether there is any association between sperm membrane integrity as determined by the hypo-osmotic swelling test score and unexplained recurrent miscarriage. DESIGN: Prospective observational study. SETTING: Tertiary referral center for recurrent miscarriage. PATIENT(S): Semen samples from 20 male partners of women who had had three or more first trimester miscarriages of unexplained etiology and semen samples from 20 prospective semen donors of unknown fertility potential. MAIN OUTCOME MEASURE(S): Sperm density, sperm motility, sperm morphology, and hypoosmotic swelling test score. RESULT(S): There was no difference in the median sperm density, the mean sperm motility, or the mean sperm morphology between the two groups. However, the recurrent miscarriage group had a significantly lower hypo-osmotic swelling test score than the control group. CONCLUSION(S): The hypo-osmotic swelling test score is significantly lower in samples from men whose partners have had unexplained recurrent spontaneous abortions. With the exception of cytogenetic abnormalities in peripheral blood karyotype, this is the first study to identify a male factor component in recurrent miscarriage.

Evaluation of the role of mitotic instability in karyotypically normal men with oligozoospermia.

OBJECTIVE: To estimate the incidence of sex chromosome aneuploidies in the somatic cells of karyotypically normal infertile men and fertile donors. DESIGN: A prospective, two-phase, controlled study. SETTING: Reproductive medicine and medical genetics units of a teaching hospital. PATIENT(S): Ten patients with oligozoospermia and 10 sperm donors with proved fertility, all with a normal karyotype 46 XY. INTERVENTION(S): Multicolor fluorescence in situ hybridization (FISH) of peripheral blood lymphocytes using a probe cocktail containing the alpha satellites DXZ1 for the X centromere and DYZ1 for the heterochromatic region of the long arm of the Y and the radiolabeled alpha satellite D18Z1 for chromosome 18. MAIN OUTCOME MEASURE(S): The incidence of sex chromosome aneuploidies in both groups. RESULT(S): A 13-fold increase in sex chromosome aneuploidies was observed in the somatic cells of infertile men with "unexplained" oligozoospermia compared to donors (P=.008). CONCLUSION(S): These findings provide suggestive evidence for the existence of an inherent mitotic instability in men with unexplained oligozoospermia.

Exaggerated effects of progestogen on uterine artery pulsatility index in Turner's syndrome patients receiving hormone replacement therapy.

OBJECTIVE: To investigate the effect of estrogen and progestogen on the resistance to blood flow in the uterine arteries of Turner's syndrome patients. DESIGN: Prospective clinical study. SETTING: A tertiary infertility clinic. PATIENTS: Five Turner's syndrome patients, six patients who had surgical castration, and five patients with idiopathic primary ovarian failure. INTERVENTIONS: The patients were treated with 2 mg E2 valerate to which 500 micrograms norgesterel was added for 10 days in a 28-day cycle. Transvaginal color Doppler was used to measure pulsatility index in the uterine arteries at eight regular intervals during a single cycle. MAIN OUTCOME MEASURE: Pulsatility index of the uterine arteries. RESULTS: The administration of norgesterel to Turner's syndrome patients resulted in an increase in pulsatility index that was significantly higher than in patients who had surgical castration (confidence interval = 0.17 to 2.42). CONCLUSION: The uterine arteries of Turner's syndrome patients are more sensitive to the tonic effect of progestogen. If manifest in cardiac arteries also this phenomenon may be partly responsible for the increased incidence of cardiovascular disease and shorter life expectancy in Turner's syndrome patients. To achieve optimal protection from cardiovascular disease, Turner's syndrome patients may benefit from hormone replacement treatment containing altered doses of estrogen and progestogen.

Effect of abnormal hypo-osmotic swelling test on fertilization rate and pregnancy outcome in in vitro fertilization cycles.

OBJECTIVE: To assess the value of the hypo-osmotic swelling test in predicting fertilization, pregnancy, implantation, miscarriage, and live birth rates in IVF-ET cycles. DESIGN: Prospective study. SETTING: Academic tertiary referral center for fertility treatment. PATIENTS: Three hundred twenty-six couples having IVF-ET for tubal damage or male factor infertility with the female partner < 38 years of age. INTERVENTIONS: Each male had a hypo-osmotic swelling test performed between 4 and 8 weeks before IVF-ET. MAIN OUTCOME MEASURES: Fertilization, implantation, miscarriage, and live birth rates. RESULTS: Eighty of 326 men had abnormal hypo-osmotic swelling tests. An abnormal test was not associated with lower fertilization rates (odds ratio [OR] = 1.14; 95% confidence interval [CI] = 0.97 to 1.14) or pregnancy rate (OR = 0.98; CI = 0.50 to 1.96). However, although couples with a normal test had a miscarriage rate of 26.9% (14/52), in the group with an abnormal test the miscarriage rate was 50.0% (7/14) (OR = 0.37; CI = 0.09 to 1.49). This resulted in a reduction in the live birth rate from 14.1% in the group with a normal test to 11.8% in patients with an abnormal test (OR = 1.23; CI = 0.45 to 3.87). CONCLUSIONS: The hypo-osmotic swelling test has little value in predicting fertilization in IVF-ET procedures. However, an abnormal test may help predict adverse outcome if pregnancy is achieved.

Outcome of triplet pregnancies resulting from IVF at Bourn Hallam 1984-1987.

43 consecutive sets of triplet pregnancies progressing beyond 16 weeks and conceived following in vitro fertilisation at the Bourn Hallam Centre between 1984-1987 were included in the study. Follow-up information was available in the 31 sets born to United Kingdom residents. 91 live births resulted at an average gestation of 33 weeks and 2 days (range 26-38 weeks). All but one of the deliveries was by Caesarean section. The average birth weight was 1.85 kg and was significantly higher in the first-born triplet than in the third (1.93 kg versus 1.74 kg, respectively). The perinatal mortality rate amongst the triplets was 32.26 per thousand births, and the neonatal death rate was 21.98 per thousand live births. This compares favourably with the latest published data on perinatal mortality rates in triplets.

The effect of progestagens on the carotid artery pulsatility index in postmenopausal women on oestrogen replacement therapy.

Part of the cardioprotective effect of postmenopausal oestrogen replacement therapy has been attributed to arterial vasodilation. This effect is partially reversed in the uterine artery by the addition of a progestagen. This study was designed to compare the effects of the C21 progestagen, dydrogesterone and the C19 testosterone derivative, norethisterone on the carotid artery pulsatility index (PI) (thought to represent distal impedance to flow) using a randomized double blind cross-over trial. The addition of progestagen resulted in a significant increase in the carotid artery PI from a median value of 1.67 during the oestrogen only phase to 1.77 (P = 0.02) during the combined phase. This trend was seen with both dydrogesterone and norethisterone, but there was no significant difference in the size of the effect caused by either progestagen. The addition of cyclical progestagen to ERT partially antagonizes the reduction in the carotid artery PI.

The evaluation of the sperm migration test as a predictor for success with intrauterine insemination.

OBJECTIVE: The objective of this study was to prospectively evaluate the sperm migration test (SMT) as a discriminator in couples undergoing intrauterine insemination (IUI). PATIENTS AND METHODS: 261 couples underwent 797 IUI treatment cycles involving gonadotropin stimulation in the three year period. All had a diagnosis of unexplained infertility. All male partners underwent a repeat standard seminal analysis and SMT prior to the female partner undergoing controlled ovarian stimulation. RESULTS: Despite apparently normal seminal analyses before referral, in 22 samples the sperm concentration, motility or morphology were abnormal (WHO criteria). Of these, 20 couples underwent 109 cycles and achieved 2 pregnancies giving a pregnancy rate of 1.8% per cycle and a cumulative pregnancy rate of 10% per couple. From the remaining couples with normal seminal analyses, 71 had an SMT <5 million/mL and 168 had an SMT >5 million/mL. The suboptimal SMT group underwent 276 cycles (3.89 cycles per couple) and achieved 18 pregnancies giving a pregnancy rate of 6.5% per cycle and a cumulative pregnancy rate of 25.4%. The normal SMT group underwent 412 cycles (2.45 cycles per couple) and achieved 60 pregnancies giving a pregnancy rate of 14.6% per cycle and a cumulative pregnancy rate of 35.7%. CONCLUSIONS: We confirm that abnormal seminal analysis leads to poor pregnancy rates with IUI. However, an SMT <5 million/mL despite normal seminal analysis (WHO criteria) also leads to significantly worse pregnancy rates. We would recommend that prior to IUI, couples are screened using the SMT.

Multicentre randomised double bind crossover trial on contamination of conventional ties and bow ties in routine obstetric and gynaecological practice.

OBJECTIVE: To assess level of contamination of neckwear worn by gynaecologists and obstetricians during routine working week. DESIGN: Multicentre randomised double blind crossover trial. Participants wore the same conventional ties for three days in one week and bow ties for the same period in second week. SETTING: Two teaching and three district general hospitals in the midlands, Wales, and north England. SUBJECTS: 15 registrars and senior registrars. INTERVENTIONS: A swab soaked in sterile saline was taken from specific area on ties at end of first and third working days and sent in transport medium for culture on chocolatised blood and MacConkey agar for 48 hours. MAIN OUTCOME MEASURES: Level of bacteriological growth assessed semiquantitatively (0 for no contamination; for heavy contamination) after swabs had been cultured. At end of study the participants completed a questionnaire to assess their attitude toward wearing different types of necktie. RESULTS: 12 doctors (80%) completed the study. Although bow ties were significantly less contaminated at end of first working day (z = -2.354, p = 0.019), this difference was not maintained; there was no difference in level of contamination on third day. Level of contamination did not increase between first and third day of wearing the same garment. One of the 10 doctors who returned the questionnaire found the bow tie very uncomfortable. All participants would consider wearing a bow tie if it proved to be less contaminated than a conventional tie. CONCLUSIONS: Although a significant difference in contamination was established between conventional and bow ties on first day of study, this difference was not confirmed on third day and there is unlikely to be any real association between tie type and bacterial contamination. Because of its negative image and difficulty to tie, the bow tie will probably remain a minority fashion.

Consecutive triplet pregnancies following in-vitro fertilization and embryo transfer. Two case reports.

The number of multiple pregnancies has been increasing as a result of the relatively widespread use of drugs for induction of ovulation and assisted conception techniques. This paper details the first reported cases of triplet pregnancies occurring in consecutive IVF cycles in two patients.

Inhibition of human spermatozoon-oocyte interaction in vitro by monoclonal antibodies to CD46 (membrane cofactor protein).

CD46 (membrane cofactor protein) is a cell surface complement regulatory glycoprotein that facilitates enzymatic cleavage of complement component C3b; it is expressed by both human oocytes and acrosome-reacted spermatozoa. Murine anti-CD46 monoclonal antibody (mAb) has been reported to decrease significantly the ability of human spermatozoa to penetrate hamster oocytes. We have investigated the effect of purified anti-CD46 mAbs on spermatozoon-oocyte interaction in an autologous zona-free oocyte penetration test. Oocytes and/or spermatozoa were preincubated with either of two anti-CD46 murine mAbs, TRA.2.10 (a non-blocking mAb) and MH61 (a mAb that functionally blocks C3b-ligand binding activity), or a control isotype-matched mAb, in medium supplemented with human serum albumin. Preincubation of both spermatozoa and zona-free oocytes with TRA.2.10, but not MH61, caused a significant decrease in the number of oocytes showing sperm binding and pronuclear formation (9/23) compared with controls (21/26) in this complement component-depleted medium. This effect was not observed if oocytes or spermatozoa alone were preincubated. These data suggest that CD46 has a role in human spermatozoon-oocyte interaction at the level of the oocyte plasma membrane, and indicate that a novel function other than direct C3b binding could be involved.

Ovarian hyperstimulation presenting as acute hydrothorax after in vitro fertilization.

Ovarian hyperstimulation that occurs with an isolated hydrothorax as the only symptom has previously been reported. We describe the second such case, the first to occur after in vitro fertilization and embryo transfer.