MicroSort® sperm sorting causes no increase in major malformation rate.

After completing this article, readers should be able to: 1. Describe the outcomes of assisted reproductive technologies (ART) for singleton, twin, and other multiple births. 2. Describe the role of fertility in adverse outcomes seen with ART births. 3. Review the association of birth defects with ART. 4. Delineate the association of disease of genomic imprinting with ART. 5. Describe the relationship between ART and the subsequent incidence of neurodevelopmental sequelae. In the 1977 ruling “Carey v. Population Services International,” the United States Supreme Court ruled that the decision to bear children is constitutionally protected. (1) Significant interest already had been shown in the development and improvements of in vitro fertilization (IVF) for infertile couples. The first human pregnancy and human birth using IVF were reported by Steptoe and Edwards in the United Kingdom. (2) Their work resulted in the first baby born via reproductive technologies, Louise Brown, born on July 25, 1978, at Oldham General Hospital in Oldham, United Kingdom. (3) She was born via a planned cesarean section, and her birthweight was 2.61 kg. The first successful viable IVF in the United States was performed by Jones and Seager-Jones in 1981 in Norfolk, Virginia. (4) Assisted reproductive technologies (ART) have seen a recent surge in popularity. The Centers for Disease Control and Prevention (CDC) reported that 122,872 cycles of ART were initiated in 2003, resulting in the delivery of 48,756 neonates, (5) accounting for approximately 1% of all neonates delivered in the United States. The percentage is higher in many countries, including Denmark, where it is estimated that 5% of all deliveries are with the assistance of ART. (6) Couples pursue ART for myriad reasons, including tubal transport factors, ovulatory dysfunction, uterine factors, endometriosis, male- and female-specific factors, and when a cause of infertility is unknown. (5) It would be very …

Novel technologies for selecting the best sperm for in vitro fertilization and intracytoplasmic sperm injection

Preimplantation genetic diagnosis (PGD) and subsequently preimplantation genetic screening (PGS) have been introduced since 1990. The difference from the already existing in vitro fertilization (IVF) technology, using intracytoplasmic sperm injection (ICSI), was the embryo biopsy at day 3 after fertilization. Although healthy children post-PGD/PGS have been born, the question of whether embryo biopsy could have any harmful effects has to be studied on large series in a prospective manner. A prospective cohort study was undertaken from 1992 until 2005, using the same approach as for the follow-up of IVF and ICSI children conceived in the same centre. Questionnaires were sent to physicians and parents at conception and at delivery. Children were examined at 2 months of age by trained clinical geneticists whenever possible. Data collected on 581 post-PGD/PGS children showed that term, birthweight and major malformation rates were not statistically different from that of 2889 ICSI children, with overall rates of major malformation among these post-PGD/PGS and ICSI children being 2.13 and 3.38%, respectively (odds ratio [OR]: 0.62; exact 95% confidence limits [95% CL]: 0.31-1.15). However, the overall perinatal death rate was significantly higher among post-PGD/PGS children compared with ICSI children (4.64 versus 1.87%; OR: 2.56; 95% CL: 1.54-4.18). When stratified for multiple births, perinatal death rates among PGD/PGS singleton and ICSI singleton children were similar (1.03 versus 1.30%; OR: 0.83; 95% CL: 0.28-2.44), but significantly more perinatal deaths were seen in post-PGD/PGS multiple pregnancies compared with ICSI multiple pregnancies (11.73 versus 2.54%; OR: 5.09; 95% CL: 2.80-9.90). The overall misdiagnosis rate was below 1%. Embryo biopsy does not add risk factors to the health of singleton children born after PGD or PGS. The perinatal death rate in multiple pregnancies is such that both caution and long-term follow-up are required.

Monozygotic triplet pregnancy following egg donation and transfer of single frozen-thawed embryo

BackgroundAzithromycin is an azalide antibiotic with an extensive range of indications and has become a common treatment option due to its convenient dosing regimen and therapeutic advantages. Human studies addressing gestational use of azithromycin have primarily focused on antibiotic efficacy rather than fetal safety. Our primary objective was to evaluate the possibility of teratogenic risk following gestational exposure to azithromycin.MethodsThere were 3 groups of pregnant women enrolled in our study: 1) women who took azithromycin. 2) women exposed to non-teratogenic antibiotics for similar indications, and 3) women exposed to non-teratogenic agents. They were matched for gestational age at time of call, maternal age, cigarette and alcohol consumption. Rates of major malformations and other endpoints of interest were compared among the three groups.ResultsPregnancy outcome of 123 women in each group was ascertained. There were no statistically significant differences among the three groups in the rates of major malformations; 3.4% (exposed) versus 2.3% (disease matched) and 3.4% (non teratogen) or any other endpoints that were examined. In the azithromycin group, 88 (71.6%) women took the drug during the first trimesterConclusionResults suggest that gestational exposure to azithromycin is not associated with an increase in the rate of major malformations above the baseline of 1–3%. Our data adds to previous research showing that macrolide antibiotics, as a group, are generally safe in pregnancy and provides an evidence-based option for health professionals caring for populations with chlamydia.

Report on management of obstructive azoospermia

Background Echinacea products are among the most popular phytomedicines on the North American market. Since at least half of all pregnancies are unplanned, many women inadvertently use echinacea in their first trimester. Presently, there is a paucity of information regarding the gestational safety of this herb. The primary objective of this study was to evaluate the safety of echinacea in pregnancy when used for upper respiratory tract ailments. Patients and Methods The study group consisted of women who were prospectively followed up after contacting the Motherisk Program regarding the gestational use of echinacea. This cohort was disease-matched to women exposed to nonteratogenic agents by maternal age, alcohol, and cigarette use. Rates of major and minor malformations between the groups were compared. Results A total of 206 women were enrolled in the study group after using echinacea products during pregnancy; 112 women used the herb in the first trimester. There were a total of 195 live births, including 3 sets of twins, 13 spontaneous abortions, and 1 therapeutic abortion. Six major malformations were reported, including 1 chromosomal abnormality, and 4 of these malformations occurred with echinacea exposure in the first trimester. In the control group, there were 206 women with 198 live births, 7 spontaneous abortions, and 1 therapeutic abortion. Seven major malformations were reported. There were no statistical differences between the study and control groups for any of the end points analyzed. Conclusions This first prospective study suggests that gestational use of echinacea during organogenesis is not associated with an increased risk for major malformations.

Objective. —To compare pregnancy outcome following first-trimester fluoxetine (Prozac) exposure with pregnancy outcome in two matched control groups. Fluoxetine is a new antidepressant used by many young women. Currently, no published data exist on its safety in pregnancy. Design. —We prospectively collected and followed up 128 pregnant women exposed to a mean daily dose of 25.8 mg (±13 mg) of fluoxetine during the first trimester and compared pregnancy outcome with two matched groups of women exposed during the first trimester of pregnancy to either nonteratogens or tricyclic antidepressants. Results. —Rates of major malformations were comparable within the three groups and did not exceed those expected in the general population. Women treated with fluoxetine had a tendency for increased risk for miscarriage when compared with women exposed to nonteratogens (relative risk, 1.9; 95% confidence interval, 0.92 to 3.92). The rate of miscarriages in the fluoxetine group was comparable with the tricyclic group (13.5% and 12.2% vs 6.8% in the nonteratogens). Conclusions. —Our study suggests that the use of fluoxetine during embryogenesis is not associated with an increased risk of major malformations. Women exposed to both fluoxetine and tricyclic antidepressants tended to report higher rates of miscarriage; further studies will be needed to confirm this observation and to separate the effects of the psychiatric condition from the associated drugs. Long-term studies will be warranted to rule out potential developmental teratology of fluoxetine, which affects a central nervous system neurotransmitter. ( JAMA . 1993;269:2246-2248)

Case-control studies have suggested that the nausea and vomiting of pregnancy (NVP) may have a protective effect against specific malformations. These suggestions have been interpreted as if the lack of NVP may put mothers at an increased teratogenic risk. A prospective, cohort-controlled study was done comparing pregnancy outcome in women not experiencing NVP with those experiencing NVP at two levels of clinical severity. Women who called the Motherisk program about first-trimester exposure to drugs and who had not experienced NVP were included as the study group. The NVP Healthline enrolled two control groups of women with NVP treated with a doxylamine-pyridoxine combination for morning sickness. These women were exposed during the first trimester of gestation to either higher than the standard dose (5-12 tablets/day) or a standard dose (1-4 tablets/day) of doxylamine-pyridoxine. The women in all three groups were followed up four to six months after the expected date of birth to ascertain pregnancy outcomes and child health. There were no major malformations among offspring of 130 women not experiencing NVP. There were two major malformations among 246 women experiencing NVP. The two control groups of women with NVP had similar distributions of gestational ages, birth rates, as well as rates of miscarriages and stillbirths, as in the no-NVP group. This study did not show an association between lack of NVP and an increase in the overall rates of major malformations.

OBJECTIVE To investigate the effects of pregestational diabetes on pregnancy outcome. METHODS Data of 126 women with pregestational diabetes prospectively collected and controlled in a single tertiary center. HbA(1C) levels at early pregnancy were registered. Adverse pregnancy outcome was defined as spontaneous abortion, congenital defect, stillbirth, or neonatal death. RESULTS There were 10 spontaneous abortions (7.9%) and 17 fetuses with congenital anomalies (13.4%), including 8 major malformations (6.3%). Compared with pregnancies with a favorable outcome, a higher HbA(1C) concentration in early pregnancy was observed in pregnancies with adverse perinatal outcome [mean (SD): 6.3 (1.6) vs. 7.2 (1.7), P=0.001]. A positive correlation between increased maternal HbA(1C) levels and the rate of fetal malformations was observed, and the group of women with poor metabolic control (early maternal HbA(1c) concentration >7%) showed a 3 to 5-fold increase in the major malformation rate. Cardiovascular and genitourinary defects accounted for 58.8% of the anomalies, and the ultrasound examinations detected seven of them (41.2%). For major malformations, the detection rate was 50% (4/8). Perinatal mortality rate was 26 per thousand (3/116). There was almost 5-fold increase in the total pregnancy loss rate in the poor control group compared with the group with fair control [22.2% vs. 5.3%, OR (95% CI): 5.1 (1.4-17.1)]. Only 11.9% of mothers used a preconception care program. CONCLUSIONS Pregestational diabetes mellitus is a significant risk factor for the developing fetus. Spontaneous abortions and congenital defects are more common when a poor metabolic control is present in early pregnancy. It is most important to improve access to preconception care programs for achieving a good metabolic control in early pregnancy. Ultrasound examinations have a low performance for detecting congenital defects in diabetic pregnancies.

Development of children born after IVF and ICSI

To assess the association between the use of medically assisted reproduction (MAR) and birth defects (BD) in newborns and terminations of pregnancy in pregnant women registered in Barcelona in the period 1992 to 2007. We studied 1905 cases and 2722 controls in a retrospective population-based case-control study. Cases comprised any newborn presenting at least one major BD, as well as any pregnancy terminated because of BD. Controls were newborns without BD. Exposure was MAR. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated by means of logistic regression to assess the association. The MAR was demonstrated to be associated with BD, after adjusting for probable confounders (aOR = 1.8; 95% CI = 1.4 to 2.5). Regarding MAR modalities, this association was statistically significant only for assisted reproduction techniques (ART) (aOR = 2.7; 95% CI = 1.8 to 4.1). In the stratified analysis by structural BD categories, frequencies for all categories were increased after ART with the exception of head-face-neck-eye defects, none after artificial insemination, and digestive-abdominal wall defects in ovulation induction. This study demonstrated a strong association between ART and BD, with an almost threefold increased risk for overall BD after ART, as compared with natural conception. Increased associations were also observed for almost all structural BD categories.

Clinical guidelines for sperm cryopreservation in cancer patients

Our objectives were to 1) determine whether first-trimester use of gabapentin is associated with an increased risk for major malformations; 2) examine rates of spontaneous abortions, therapeutic abortions, stillbirths, mean birth weight and gestational age at delivery; and 3) examine rates of poor neonatal adaptation syndrome following late pregnancy exposure. The study design was prospective. Women were included who initially contacted the services between 5 and 8 weeks with a comparison group of women exposed to nonteratogens, collected in a similar manner. We have data on 223 pregnancy outcomes exposed to gabapentin and 223 unexposed pregnancies. The rates of major malformations were similar in both groups (p = 0.845). There was a higher rate of preterm births (p = 0.019) and low birth weight <2,500 g (p = 0.033) in the gabapentin group. Among infants who were exposed to gabapentin up until delivery, 23 of 61 (38%) were admitted to either the neonatal intensive care unit or special care nursery for observation and/or treatment, vs 6 of 201 (2.9%) live births in the comparison group (p < 0.001). There were 2 cases of possible poor neonatal adaptation syndrome in neonates exposed to gabapentin close to delivery, compared with none in the comparison group, although it must be noted that these infants were concomitantly exposed to other psychotropic drugs. Among the women who took gabapentin, the major indications were pain (n = 90; 43%) and epilepsy (n = 71; 34%); the remainder were for other indications, mostly psychiatric. Our results suggest that although this sample size is not large enough to make any definitive conclusions, and there was no comparator group treated with other antiepileptic drugs, gabapentin use in pregnancy does not appear to increase the risk for major malformations. This finding and the increased risk for low birth weight and preterm birth require further investigation.

The safety of omeprazole during pregnancy: A multicenter prospective controlled study