Chromosome analysis of spontaneous abortions after IVF. A European survey

A European survey was carried out in order to evaluate the incidence of chromosome anomalies in spontaneous abortions after IVF. Of the 34 abortuses analysed, 21 had a chromosome anomaly (62%), namely three with monosomy X,14 autosomal trisomies, one double trisomy, one triploidy, one tetraploidy and one translocation. These data show that IVF does not increase the incidence of chromosomal abortuses when compared with natural conceptions (60%).     

Multiple pregnancy after in-vitro fertilization and embryo transfer: report of a quadruplet pregnancy and delivery

The first baby from in-vitro fertilization (IVF) was born in England in 1978 as a result of retrieval of a single preovulatory oocyte in the course of a natural cycle (Steptoe and Edwards, 1978). At present most programmes of IVF throughout the world do not use natural cycles producing only one oocyte, but rather multiple oocyte cycles produced by clomiphene citrate (CC), human menopausal gonadotrophin (HMG), or pure follicle stimulating hormone (FSH), either separately or in combination, sequentially or concomitantly, for the induction of multiple follicular maturation.     

Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women

BACKGROUND: Obesity is increasing rapidly among women all over the world. Obesity is a known risk factor for subfertility due to anovulation, but it is unknown whether obesity also affects spontaneous pregnancy chances in subfertile, ovulatory women. METHODS: We evaluated whether obesity affected the chance of a spontaneous pregnancy in a prospectively assembled cohort of 3029 consecutive subfertile couples. Women had to be ovulatory and had to have at least one patent tube, whereas men had to have a normal semen analysis. Time to spontaneous ongoing pregnancy within 12 months was the primary endpoint. RESULTS: The probability of a spontaneous pregnancy declined linearly with a body mass index (BMI) over 29 kg/m(2). Corrected for possible related factors, women with a high BMI had a 4% lower pregnancy rate per kg/m(2) increase [hazard ratio: 0.96 (95% CI 0.91-0.99)]. CONCLUSIONS: These results indicate that obesity is associated with lower pregnancy rates in subfertile ovulatory women.     

IVF of mouse ova in a simplex optimized medium supplemented with amino acids

The addition of amino acids to a modified simplex optimized medium (mKSOM) did not increase the percentage of blastocysts that develop from CF1 mouse ova fertilized in vitro. In contrast, the percentage of blastocysts that began to hatch and the number of cells in these blastocysts, particularly in the inner cell mass, was increased. The added amino acids also supported the development of a more organized extracellular matrix in the same blastocysts. The results suggest that zygotes produced in amino acid-supplemented mKSOM have a greater developmental potential, perhaps developing at a faster rate, than zygotes produced in mKSOM. This enhanced developmental potential may be caused by the alleviation of osmotic stress on the ova and zygotes by the amino acids that are osmolytes. The fertilization of human ova in vitro may benefit from the inclusion of free amino acids in the fertilizing medium. The availability of a medium that can be used to support both IVF and preimplantation development in the mouse is likely to benefit the recovery of mouse strains from cryopreserved spermatozoa.     

Simplifying assisted conception techniques to make them universally available--a view from India.

In-vitro fertilization and related assisted conception techniques are beyond the reach of most infertile couples in India because they are so expensive. Recent innovations such as the use of the natural cycle, the techniques of gamete intra-Fallopian transfer, intravaginal culture and transcervical oocyte--sperm transfer, vaginal ultrasound-guided oocyte retrieval and the availability of ready-to-use culture medium have helped to simplify assisted conception. Research today should focus on further developing these techniques so that better pregnancy rates can be achieved with them. These simplified inexpensive assisted conception techniques can then be adapted for conditions in the developing world, so that infertile patients the world over can benefit from them.     

Multiple-birth risk associated with IVF and extended embryo culture: USA, 2001

BACKGROUND: Multiple births are associated with serious adverse infant and maternal outcomes. The objective of this study was to assess the multiple-birth risk (MBR) associated with IVF and determine whether the risk is impacted by stage of embryo development at transfer. METHODS: A population-based sample of 50 819 IVF transfers utilizing day 3 or day 5 embryos performed in the USA in 2001 on women aged 20-40 years was used to assess MBR and live-birth rate (LBR), stratified by patient age, supernumerary embryo availability, and number of embryos transferred. RESULTS: Although significantly more day 5 than day 3 transfers used < or =2 embryos (69.2 versus 27.7%), the former were not associated with decreased MBR. MBR was high when >1 embryo was transferred, irrespective of embryo development stage. LBR were generally maximized with 2 embryos transferred, and for some (day 5 transfers, patients aged 35-37 years) with one embryo. Electing to transfer a single day 5 embryo appeared efficacious for some patients: women aged 20-37 years with supernumerary embryos cryopreserved had LBR of 31.6-39.5%. CONCLUSIONS: MBR is high when > or =2 embryos are transferred. Single embryo transfer is the only way to prevent many multiple births and associated adverse health outcomes.     

Monozygotic twinning associated with day 5 embryo transfer in pregnancies conceived after IVF

BACKGROUND: This study examines the association between day of embryo transfer and monozygotic (MZ) twinning. METHODS: We used a population-based sample of 108,36 IVF/embryo transfer procedures in which the patients oocytes' were freshly fertilized (non-frozen; non-donor) and 39,98 resultant pregnancies from US clinics in 1999 and 2000. Cases were pregnancies for which the number of fetal hearts observed on ultrasound exceeded the number of embryos transferred. These pregnancies were considered to contain at least one set of MZ twins. A total of 226 MZ pregnancies were compared with two control groups: 23,880 singleton pregnancies (one fetal heart) and 15,092 other multiple-gestation pregnancies (> or = 2 fetal hearts but the number of fetal hearts on ultrasound was less than or equal to the number of embryos transferred). RESULTS: Cases of presumed MZ multiple-gestation pregnancies were more likely to have had a day 5 embryo transfer compared with day 3 embryo transfers than singleton pregnancies [adjusted odds ratio (AOR) = 3.92, 95% confidence interval (CI) = 2.97-5.17] or other multiple-gestation pregnancies (AOR = 3.91, 95% CI = 2.96-5.17) conceived with IVF/embryo transfer. CONCLUSIONS: Day 5 embryo transfer may be associated with increased MZ twinning.     

Successful pregnancy and birth after IVF in a woman with cystic fibrosis

As survival increases, patients with cystic fibrosis (CF) are often confronted with reproductive issues. Initial reports gave conflicting advice regarding the outcome of pregnancy in CF. However a recent large longitudinal study of pregnancies in CF women suggested that pregnancy has little impact on morbidity or mortality. Reduced fertility in CF women has been described, possibly due to thickened cervical mucus, and intrauterine insemination (IUI) has been used to overcome this. We report the first woman with CF, to our knowledge, to be successfully treated with IVF after repeated failed attempts at IUI.     

Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review

BACKGROUND: Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. METHODS: Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. CONCLUSION: Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases.     

The dygynic origin of a triploid fetus from an IVF pregnancy

The case of an IVF pregnancy that resulted in an aborted tnploidembryo with 69,XXY karyotype is reported. The analysis of DNApolymorphisms shows that the event is due to a maternal secondmeiotic non-disjunction.     

Pregnancy and birth resulting from transfer of a blastocyst observed to have one pronucleus at the time of examination for fertilization.

This case report describes a successful full-term pregnancy and birth after the transfer of a zona-free blastocyst derived from an oocyte observed at fertilization check as having only one distinct pronucleus (PN). The patient had previously undergone four in-vitro fertilization (IVF) cycles and three frozen embryo transfer cycles, with one pregnancy resulting. In this IVF cycle, 7/19 oocytes were fertilized exhibiting two distinct PN; however, all these oocyctes failed to develop in culture and had arrested or totally fragmented by day 6 after insemination. One oocyte (1/19) displayed only one PN 18 h after insemination, but culture of this oocyte led to development of an early cavitating blastocyst by day 6. Since no other embryos were available for transfer to the patient, this embryo was transferred, resulting in a full-term pregnancy with delivery of a normal healthy boy. Observation of a single PN at the normal time of fertilization assessment would not appear to be an absolute indicator of developmental incompetence. In-vitro culture to 6 days post-insemination provides the opportunity to assess embryological development after activation of the embryonic genome. Formation of a morphologically normal blastocyst may be an indicator of a fertilized embryo with normal developmental capacity.     

Health care costs resulting from IVF: prenatal and neonatal periods

BACKGROUND: The use of expensive infertility treatments is increasing rapidly. To compare the prenatal and neonatal health care costs after IVF and spontaneous conception, we conducted a study based on a cohort of IVF and control pregnancies and neonates. METHODS: A cohort of 215 IVF mothers and 255 IVF neonates were compared with a cohort of 662 control mothers and 388 control children, randomly chosen from the Finnish Medical Birth Register and matched for sex, year of birth, area of residence, parity, maternal age, socioeconomic status and plurality. The analyses on prenatal and neonatal costs were performed by plurality. Singletons were also compared with twins. The cost calculations were based on the known level of utilization of maternal and neonatal health care services. RESULTS: The total health care costs for an IVF singleton until the end of the neonatal period were 5780 and 15 580 for an IVF twin. The health care costs were 1.3-fold for IVF singletons and 1.1-fold for IVF twins compared to control singletons and twins. The costs for twins were approximately 3-fold compared to singletons. CONCLUSIONS: The health care costs of an IVF singleton neonate were higher than those of a spontaneously conceived control neonate with similar backgrounds. For twins the health care costs were equal. Multiple births increase the health care costs and therefore the reduction of multiple pregnancies is the most effective way to reduce the health care costs resulting from IVF.     

Spontaneous conception and intrauterine pregnancy in a symptomatic missed abortion of ectopic pregnancy conceived in the previous cycle

We encountered a rare case of combined intrauterine and extrauterinepregnancy that occurred following separate spontaneous ovulations.A 33 year old woman visited our hospital with the chief complaintof abdominal pain on April 16, 1993. Her last menstruation wasfrom March 23 for 6 days. However, the urinary human chorionicgonadotrophin (HCG) on April 19 was 1024 IU/L Pelvic examinationand ultrasonography indicated an extrauterine pregnancy, whichwas confirmed by laparotomy and histo-logical identificationof trophoblast cells. The urinary HCG concentration markedlydecreased after the operation. However, the HCG level increasedagain on the fifth postoperative day, and a gestational sac(11 mm) was identified in the uterine cavity on the 11th post-operativeday, indicating that this intrauterine pregnancy was establishedfollowing spontaneous ovulation which occurred before the removalof the extrauterine pregnancy. This case indicates that a combinedpregnancy can occur not only after simultaneous multiple ovulationsbut also after the separate spontaneous ovulations.     

Sequential genetic events leading to conjoined twins in a monozygotic triplet pregnancy

A rare case of conjoined twins in a triplet pregnancy is presented.Selective termination was attempted. After termination of thepregnancy, deoxyribonucleic acid fingerprinting revealed a monozygoticorigin for all three fetuses.     

Three blastocyst stage embryo transfer resulting in a quintuplet pregnancy

High-order pregnancies are associated with high morbidity and mortality and the incidence is increased as a drastic complication of assisted reproductive technology. This case presents a high-order pregnancy achieved by transfer of three blastocyst stage embryos resulting in a quintuplet pregnancy including a monochorionic triplet. Following the selective termination of the monochorionic triplet, two healthy children were born. The mechanism of monochorionic development and its association with assisted reproductive technology are discussed.     

Cumulative conception and live birth rates in natural (unstimulated) IVF cycles

IVF treatment, which involves ovarian stimulation, poses significant health problems such as ovarian hyperstimulation and is associated with a high incidence of multiple pregnancy and premature birth. In this paper, we demonstrate how natural cycle IVF is an effective and potentially cost-effective alternative treatment option for certain groups of infertile couples. The study was conducted in the Assisted Conception Unit at King's College School of Medicine, London. Fifty-two women with regular menstrual cycles whose partners had normal semen parameters were offered a total of 181 cycles of treatment (average 3.49 per couple). Life table analysis was used to calculate cumulative success rates after successive cycles of treatment. After four cycles, the cumulative probability of pregnancy was 46% with an associated live birth rate of 32%. To achieve maximal effectiveness, natural cycle IVF should be offered as a series of treatment cycles, for it is safer, less stressful and can be offered over consecutive cycles. Moreover, the avoidance of expensive drugs and reduced intensity of monitoring make natural cycle IVF less expensive than conventional treatment involving stimulation. We calculate that this treatment can be offered at approximately 23% of the cost of a stimulated cycle, suggesting that it may be a cost-effective alternative to conventional assisted conception techniques.     

Inhibins and activins in human ovulation, conception and pregnancy

The activins and inhibins are glycoproteins that belong to thetransforming growth factor-ß superfamily, and, assuch, have diverse effects at many stages during growth anddevelopment. Originally identified by their effects on folliclestimulating hormone in males and females, the recent developmentof specific and sensitive assays for this group of polypeptideshas permitted the elucidation of their role in 'fine-tuning'the hypothalamic-pituitary-gonadal axis. This review articlefocuses on the roles of inhibin and activin in female reproductivephysiology with reference to possible future clinical applicationsin the investigation of infertility and abnormal pregnancy.     

Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study

BACKGROUND: The Dutch IVF guideline suggests triage of patients for IVF based on diagnostic category, duration of infertility and female age. There is no evidence for the effectiveness of these criteria. We evaluated the predictive value of patient characteristics that are used in the Dutch IVF guideline and developed a model that predicts the IVF ongoing pregnancy chance within 12 months. METHODS: In a national prospective cohort study, pregnancy chances after IVF and ICSI treatment were assessed. Couples eligible for IVF or ICSI were followed during 12 months, using the databases of 11 IVF centres and 20 transport IVF clinics. Kaplan-Meier analysis was performed to estimate the cumulative probability of an ongoing pregnancy, and Cox regression was used for assessing the effects of predictors of pregnancy. RESULTS: 4928 couples starting IVF/ICSI treatment were prospectively followed. On average, couples had 1.8 cycles in 12 months for both IVF and ICSI. The 1-year probability of ongoing pregnancy was 44.8% (95% CI 42.1-47.5%). ICSI for severe oligospermia had a significantly higher ongoing pregnancy rate than IVF indicated treatments, with a multivariate Hazard ratio (HR) of 1.22 (95% CI 1.07-1.39). The success rates were comparable for all diagnostic categories of IVF. The highest success rate is at age 30, with a slight decline towards younger women and women up to 35 and a sharp drop after 35. Primary subfertility with a HR of 0.90 (95% CI 0.83-0.99) and duration of subfertility with a HR of 0.97 (95% CI 0.95-0.99) per year significantly affected the pregnancy chance. CONCLUSIONS: The most important predictors of the pregnancy chance after IVF and ICSI are women's age and ICSI. The diagnostic category is of no consequence. Duration of subfertility and pregnancy history are of limited prognostic value.     

Pregnancy: Effects of a behavioural rhythm on conception probability and pregnancy outcome

This paper concerns a behaviour-driven weekday rhythm in conceptionrates in a large natural human population. From 1978 to 1991,North Carolina normal live single births arose from menstrualcycles which began on Monday in clear excess over other weekdays.Cycles beginning on Friday were also in excess. Cycles startingon Saturday and Sunday, or Wednesday and Thursday, each representedsignificantly less than one in seven of weekly totals. The sourceof the observed synchrony was a Sunday morning peak of coitalfrequency. Average cycles which began on Monday had their mostfertile day on the most likely day for intercourse, translatinga weekly insemination rhythm into a weekly conception rate rhythm.The secondary conception peak in Friday-onset cycles increasedwith age, to become the major peak for mothers aged >30 years.We interpret this to represent a previously unreported secondtype of cycle with a modal follicular phase length of 10 days,the frequency of which increases with age. Several large groupsof anomalous human births depart significantly from the weekdayrhythm of normal conceptions. These outcomes parallel resultsof experimental interference with fertilization timing in estruativemammals. We believe that this implicates anomalous fertilizationtiming in several of the most numerous anomalies of human prenataldevelopment.     

Successful outcome of multifetal reduction in a pregnancy with 12 live fetuses

Multifetal reduction of 12 live fetuses enabled the successfuldelivery of a healthy pretern baby in a patient treated withhuman menopausal gonadotrophin/human chorionic gonadotrophin.