Are spermatid injections into human oocytes now mandatory?
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Cell Cycle↗
Biomedical subjects
S L Tan
Publications and source records attributed to S L Tan.
Factors influencing the outcome of in-vitro fertilization with epididymal spermatozoa in irreversible obstructive azoospermia.
Microsurgical epididymal sperm aspiration (MESA) and in-vitro fertilization (IVF) were found to offer limited opportunity for fatherhood to 45 men with obstructive azoospermia, due principally to poor embryo implantation. Adequate sperm preparations were obtained in 46/50 treatment cycles (92%), with the best motility found in the caput epididymis in 89% of cases. The mean fertilization rate was 11.2% and fertilization occurred in 23 cycles (50%), with embryo transfer arising from 12/26 men with vas aplasia (CAV), 4/9 with genital tract obstruction (EV) and 7/11 with irreversible vasectomy (VV). The overall implantation rate was low, 8.7% per embryo transfer (11.7% per 2-3 embryo transfers) and was not improved by Fallopian transfer. There were two pregnancies (4% per cycle), both in the EV group where embryo formation and implantation (2/4, 50% per cycle) were optimum even though sperm preparations were paradoxically inferior to the CAV and VV groups. The spermatozoa retrieved in the two successful EV cycles were appreciably blood contaminated. Analysis of the 21 failed embryo transfers showed delayed fertilization in 10 cycles, cystic fibrosis (CF) mutation or familial disease in 7/12 CAV men and the VV men were older (P < 0.001). A pregnancy which miscarried arose from a case of Young's syndrome, a carrier of CF mutation DF508. Male factors could thus be implicated in the high embryo wastage of MESA cycles and might also be influencing implantation in other IVF procedures. Where feasible, male reconstructive surgery is preferable unless fertilization can be improved, possibly by speedier retrieval techniques or by permitting sperm capacitation in vitro, but probably more effectively by micro-assisted insemination.
Adult↗
Simplifying in-vitro fertilization therapy.
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Clinical Protocols↗
Luteinizing hormone-releasing hormone agonists for ovarian stimulation in assisted reproduction.
Although the use of luteinizing hormone-releasing hormone (LHRH) agonists and human menopausal gonadotropin (hMG) for ovarian stimulation in assisted reproduction has gained widespread popularity, a number of major issues regarding their use remain unresolved. Some of these issues are examined in the light of recent developments. The routine use of LHRH agonists produces significantly higher pregnancy and livebirth rates compared with conventional methods of ovarian stimulation. A number of prospective, randomized studies have shown that the long protocol of LHRH agonist administration is superior to the short and ultrashort protocols, and it appears that early follicular phase initiation of the long protocol may be particularly beneficial. Another major advantage of the long protocol of LHRH agonist administration is that, with its use, precise timing of human chorionic gonadotropin (hCG) administration is not important. It would, therefore, appear that the routine use of LHRH agonists has both medical as well as practical advantages.
Abortion, Spontaneous↗
Fertilisation by testicular sperm with standard IVF techniques.
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Cleavage Stage, Ovum↗
Excess concepti compared with number of embryos transferred in in vitro fertilization.
To reduce the risk of multiple pregnancy, most in vitro fertilization programs limit the number of embryos transferred; because monozygotic twinning may occur, it is possible that more concepti are produced than the number of embryos transferred. To quantify the prevalence of this phenomenon, 1820 clinical pregnancies generated from 11,601 in vitro fertilization treatment cycles were reviewed. Two patients conceived four fetuses each after having had three embryos transferred, while one conceived three fetuses after having had two embryos transferred. The overall prevalence rate was, therefore, one in 607 cases. The obstetric details of these three pregnancies are reported.
Journal Article↗
Reaction-frequencymetric method: a new analytical technique for determination of submicromolar concentration levels of vitamin C.
A new analytical technique for the assay of pharmaceutical substances at low concentration levels has been proposed and applied to the determination of vitamin C as an example of its application. It is based on the chemical reaction of vitamin C with iodine in a sodium citrate-hydrochloric acid medium, followed by measurement of the frequency change of a silver-plated piezoelectric quartz crystal. The frequency change is proportional to the vitamin C concentration from 2 x 10(-7) to 4 x 10(-6) M. The method was applied to the assay of vitamin C in pharmaceutical preparations.
Ascorbic Acid↗
The use of the stimulated acrosome reaction test as a test of fertilizing ability in human spermatozoa.
OBJECTIVE: To assess if patients who do not fertilize human oocytes in vitro can be identified by a lack of acrosomal response of their spermatozoa to stimulation by the calcium ionophore A23187. DESIGN: The stimulated acrosomal response for all patients was calculated. Those not achieving fertilization were compared with a normogram constructed from donors and patients who achieved fertilization; the 0.5th centile (31.3% increase in the number of spermatozoa reacted) was used as a discriminant point. PATIENTS: Fifty-four IVF patients and 15 fertile sperm donors. SETTING: An outpatient based IVF program. INTERVENTIONS: Acrosome reaction stimulated by 2 hours incubation in a 5-mumol/L solution of the calcium ionophore A23187. RESULTS: Patients who fertilized oocytes responded as donors. Eight of 16 patients failing to fertilize oocytes showed a minimal increase in the number of acrosome-reacted spermatozoa (mean [+/- SD] rise 6.3% +/- 10.3%). An acrosomal response of < 31.3% predicts fertilization failure in 100% of cases. CONCLUSIONS: Failure of the acrosome to react is responsible for some failure of IVF.
Acrosome↗
Effects of age, gravidity and male infertility status on cumulative conception rates following artificial insemination with cryopreserved donor semen: analysis of 2998 cycles of treatment in one centre over 10 years.
The effects of age, gravidity and male infertility status on cumulative conception rates after donor insemination were investigated in an analysis of 2998 treatment cycles undertaken on 443 patients. It was found that the cumulative conception rates after 3, 6 and 12 cycles of treatment were 21, 40 and 62% respectively for patients < 30 years of age compared with 17, 26 and 44% for those aged > or = 30 years (P = 0.008). There was also a significant difference (P < 0.001) in results depending on course of treatment and the cumulative conception rates were 19% after 3 cycles, 33% after 6 cycles and 54% after 12 cycles of treatment in the first course of treatment compared with 40, 67 and 79% respectively in those who returned for subsequent courses of treatment after having achieved a donor insemination pregnancy in the first treatment course. Gravidity and male infertility status (azoospermia or oligozoospermia/asthenozoospermia) did not significantly affect the cumulative conception rates.
Adult↗
Pregnancy using spermatozoa aspirated from the vas deferens in a patient with ejaculatory failure due to spinal injury.
Aspiration of the vas deferens under local anaesthesia was carried out in a man with ejaculatory failure due to tetraplegia after rectal electrostimulation had failed to provide an ejaculate satisfactory for use in in-vitro fertilization. After passage through a discontinuous Percoll gradient and exposure to 3 mmol pentoxifylline and 3 mmol 2-deoxyadenosine, the final preparation consisted of 50,000 spermatozoa with 4% progressive motility. This was sufficient for the insemination of seven of the 23 oocytes that were collected from the patient's wife by transvaginal ultrasound-guided follicular aspiration. Three high-grade embryos were produced which were transferred transcervically into the uterus 2 days later. A singleton pregnancy resulted which is currently ongoing at 30 weeks gestation. Aspiration of the vas deferens is a relatively simple technique which provides an acceptable alternative to rectal electrostimulation, artificial sperm reservoirs and donor insemination in patients with ejaculatory failure.
Adult↗
A controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization.
The outcome of in-vitro fertilization and embryo transfer (IVF-ET) was compared in 76 patients with polycystic ovaries (PCO) diagnosed on pre-treatment ultrasound scan, and 76 control patients who had normal ovaries and were matched for age, cause of infertility and stimulation regimen. Despite receiving significantly less human menopausal gonadotrophin (HMG), patients with PCO, as compared with controls, had significantly higher serum oestradiol levels on the day of human chorionic gonadotrophin administration (5940 +/- 255 versus 4370 +/- 240 pmol/l, P < 0.001), developed more follicles (14.9 +/- 0.7 versus 9.8 +/- 0.6, P < 0.001) and produced more oocytes (9.3 +/- 0.6 versus 6.8 +/- 0.5, P = 0.003). However, fertilization rates were reduced in the PCO patients (52.8 +/- 3.4% versus 66.1 +/- 3.4%, P = 0.007). There was no significant difference in cleavage rates. The pregnancy rate/embryo transfer was 25.4% in the PCO group and 23.0% in the group with normal ovaries. There were three high order multiple pregnancies in the PCO group compared with none in the group with normal ovaries. Of the PCO patients, 10.5% developed moderate/severe ovarian hyperstimulation syndrome (OHSS) compared with none of the controls (P = 0.006). Patients with and without PCO undergoing IVF have comparable pregnancy and livebirth rates. However, it is important to diagnose PCO before ovarian stimulation is initiated as these patients are more likely to develop moderate or severe OHSS following IVF-ET.
Adult↗
Acrosome reactivity in spermatozoa of different morphology in response to stimulation with follicular fluid.
The ability of the morphologically abnormal spermatozoon to undergo the processes necessary for fertilization is unknown; one of the essential processes is the acrosome reaction. In order to assess this, spermatozoa from 10 known fertile donors were incubated with either follicular fluid or Earle's medium containing 3 mg/ml bovine serum albumin at 37 degrees C for 6 h. The spermatozoa were then stained with 2% Trypan Blue prior to being fixed in glutaraldehyde and stained for the presence of the acrosomal cap using the triple stain. Fifty live spermatozoa in each of four morphological categories (normal head, large head, small head, abnormal neck or tail) were examined and the number of acrosome-reacted spermatozoa determined. There was a significant difference between the morphological groups in the baseline number of acrosome-reacted spermatozoa, determined by examining sperm samples incubated in Earle's medium; however, the number of spermatozoa undergoing the acrosome reaction in response to stimulation with follicular fluid (i.e. the number of spermatozoa acrosome-reacted in follicular fluid minus the number acrosome-reacted in Earle's medium) was similar for all morphological groups. This suggests that abnormal sperm morphology did not affect the response of spermatozoa to activation of the acrosome reaction by exogenous stimuli.
Acrosome↗
Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin.
To assess the risk of miscarriage after in-vitro fertilization (IVF) with respect to age, cause of infertility, ovarian morphology and treatment regimen, a retrospective analysis was performed of the first 1060 pregnancies conceived between June 1984 and July 1990 as a result of 7623 IVF cycles. Superovulation induction was achieved with human menopausal gonadotrophin (HMG) and/or purified follicle stimulating hormone (FSH) together with either clomiphene citrate or the gonadotrophin hormone-releasing hormone (GnRH) agonist buserelin, the latter either as a short 'flare' regimen or as a 'long' regimen to induce pituitary desensitization. There were 282 spontaneous abortions (26.6%) and 54 ectopic pregnancies (5.1%). The mean age of women with ongoing pregnancies was 32.2 (SD 3.9) years compared with 33.2 (SD 4.1) years in those who miscarried, which were significantly different (P = 0.008). There was no relation between the miscarriage rate and the indication for IVF. The miscarriage rate was 23.6% in women with normal ovaries compared with 35.8% in those with polycystic ovaries [P = 0.0038, 95% confidence interval (CI) 4.68-23.10%]. There was no difference in the miscarriage rate between treatment with HMG or FSH. Women whose ovaries were normal on ultrasound were just as likely to miscarry if they were treated with clomiphene or with the long buserelin protocol. Those with polycystic ovaries, however, had a significant reduction in the rate of miscarriage when treated with the long buserelin protocol, 20.3% (15/74), compared with clomiphene citrate, 47.2% (51/108) (P = 0.0003, 95% CI 13.82-40.09%).
Abortion, Spontaneous↗
The influence of the number of embryos transferred in 1060 in-vitro fertilization pregnancies on miscarriage rates and pregnancy outcome.
To assess the incidence of miscarriage, multiple pregnancy and outcome of pregnancy in relation to the number of embryos transferred during in-vitro fertilization (IVF), an analysis was performed of 1060 pregnancies conceived in a tertiary-referral IVF clinic. There was no difference in the miscarriage rate after transfer of one or two embryos (37.7% and 34.6%), or after three or four embryos (22.5% and 25.2%). The miscarriage rate was, however, higher when one or two embryos were transferred compared with three (P < 0.01) or four embryos (P < 0.02). Of the 724 ongoing pregnancies, 524 (72.3%) were singleton, 164 (22.7%) twin, 33 (4.6%) triplet and three (0.4%) quadruplet. The mean (+/- SD) ages of women with singleton, twin, triplet and quadruplet pregnancies were 32.5 (+/- 3.8), 32.0 (+/- 3.5), 29.76 (+/- 4.3) and 29.67 (+/- 2.5) years respectively. The mean age of women with singleton and twin pregnancies was similar and both were greater than that of triplet pregnancies (P < 0.007). The overall perinatal mortality rate (PNMR) was 39.7/1000. The PNMR for singletons was 17.2/1000, for twins 80.0/1000 and for triplets 30.6/1000. All of the babies from the three quadruplet pregnancies survived. There were more babies lost in the twin pregnancies than any other group, although this only reached significance for singletons versus twins (P < 0.00005). We conclude that the incidence of miscarriage is increased in women in whom one or two embryos are transferred. Multiple pregnancies are more likely to occur in younger women and are associated with a significantly higher rate of perinatal mortality.
Abortion, Spontaneous↗
Hypersecretion of luteinising hormone: a significant cause of infertility and miscarriage.
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Abortion, Spontaneous↗
Cumulative conception and livebirth rates after in-vitro fertilisation.
Cumulative conception and livebirth rates related to age and cause of infertility provide the most useful estimate of success after in-vitro fertilisation (IVF), but limited data are available. It is also uncertain whether the probability of pregnancy, livebirth, and pregnancy failure changes with repeated treatment cycles. To assess the effects of patients' age and cause of infertility on these outcomes, we studied the results of 5055 consecutive IVF cycles (773 clinical pregnancies, 518 livebirths) undertaken on 2735 patients in a single IVF unit. Cumulative conception and livebirth rates were analysed by the life-table approach and differences in rates between age-groups and between causes of infertility were measured by the log-rank test and logistic regression modelling. Both conception and livebirth rates per cycle declined with age (p less than 0.001), and cumulative conception and livebirth rates after five treatment cycles were about 54% and 45%, respectively, at 20-34 years, compared with 38.7% and 28.9% at 35-39 years and 20.2% and 14.4% at greater than or equal to 40 years. The two rates were significantly different between causal groups (p less than 0.001 and p = 0.02, respectively) and were lowest in patients with male infertility or multiple infertility factors. The pregnancy failure rate was higher (p = 0.006) in women over the age of 34 years and there was a significant decline in the chances of pregnancy and livebirth per cycle with successive treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies.
OBJECTIVE: To compare the obstetric outcome of in vitro fertilization pregnancies with normally conceived pregnancies. STUDY DESIGN: The obstetric outcome of in vitro fertilization pregnancies achieved in 763 British residents at two in vitro fertilization clinics resulting in the births of 961 babies were compared by means of the relative risk statistic with a control group of naturally conceived primiparous pregnancies matched by maternal age and multiplicity of pregnancy. RESULTS: Twenty-five percent of in vitro fertilization pregnancies were multiple pregnancies. The incidence of singleton term breech presentation was similar to that among controls. As compared with controls there was an increased incidence among in vitro fertilization pregnancies of vaginal bleeding and hypertension requiring hospitalization (p less than 0.001) and cesarean births (p less than 0.001) and, among in vitro fertilization singleton pregnancies, an increased incidence of intrauterine growth retardation (p less than 0.05), placenta previa (p less than 0.05), and preterm delivery (p less than 0.001). The congenital malformation, stillbirth, and perinatal mortality rates were comparable with maternal age-standardized national rates. CONCLUSIONS: Although the majority of in vitro fertilization pregnancies have a satisfactory obstetric outcome, there are a number of increased obstetric risks that may reflect the history of infertility, the relatively high incidence of poor obstetric history, and the lower threshold for obstetric intervention in in vitro fertilization patients.
Adult↗
The use of transvaginal color flow imaging after in vitro fertilization to identify optimum uterine conditions before embryo transfer.
OBJECTIVE: To assess whether a measure of uterine blood flow impedance (the pulsatility index, PI) as determined by transvaginal ultrasonography with color blood flow imaging, may be used to assess endometrial receptivity immediately before the time of embryo transfer (ET) after assisted conception. DESIGN: A prospective study of infertile women who had undergone treatment to induce multiple follicular development followed by ultrasound-guided oocyte retrieval. The oocytes were fertilized in vitro. SETTING: The Hallam Medical Centre. PATIENTS: Eight-two women (22 to 44 years of age) who all had three or four good quality embryos available for transfer to the uterus. INTERVENTIONS: All women were examined by transvaginal ultrasonography, with color flow imaging and blood flow analysis, immediately before ET. MAIN OUTCOME MEASURES: The mean PI of the left and right uterine arteries, the pregnancy rate (PR) (%), the embryo implantation rate (%), and the multiple PR (%). RESULTS: The patients were grouped according to whether the PI was low (1.00 to 1.99), medium (2.00 to 2.99), or high (3+). There were 27 women in the low PI group, 36 in the medium, and 19 in the high. The PR (%), embryo implantation rate (%), and multiple PR (%) were 41%, 15.3%, and 27.3% for the low PI group and 47%, 22.2%, and 47.1% for the medium PI group. There were no pregnancies in the high PI group. Thus 35% (19/54) of women who failed to become pregnant had a PI value greater than 3.0. CONCLUSIONS: These data suggest that the PI value on the day of ET could be used to: (1) increase the implantation rate by showing which embryos should be cryopreserved until the uterus is more receptive and (2) reduce the multiple PR by indicating that the number of embryos transferred should be limited when the uterus is most receptive.
Embryo Transfer↗