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PubMed1994

The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence.

BACKGROUND: Although the medical complications associated with multiple-gestation pregnancies have been well documented, little is known about the effects of such pregnancies on the use of health care resources and the associated costs. This is an important issue because of the increasing use of assisted-reproduction techniques, which commonly result in multiple-gestation pregnancies. METHODS: We determined hospital charges and the use of assisted-reproduction techniques (such as induction of ovulation, in vitro fertilization, and gamete intrafallopian transfer) for 13,206 pregnant women (11,986 with singleton pregnancies, 1135 with twin pregnancies, and 85 with more than two fetuses) who were admitted for delivery to Brigham and Women's Hospital, Boston, in 1986 through 1991 and their 14,033 neonates (11,671 singletons, 2144 twins, and 218 resulting from higher-order multiple gestations). RESULTS: After we controlled for variables known to affect hospital charges, the predicted total charges to the family in 1991 for a singleton delivery were $9,845, as compared with $37,947 for twins ($18,974 per baby) and $109,765 for triplets ($36,588 per baby). Assisted-reproduction techniques were used in 2 percent of singleton, 35 percent of twin, and 77 percent of higher-order multiple-gestation pregnancies; such procedures were approximately equally divided between induction of ovulation alone and in vitro fertilization or gamete intrafallopian transfer. CONCLUSIONS: Multiple-gestation pregnancies, a high proportion of which result from the use of assisted-reproduction techniques, dramatically increase hospital charges. If all the multiple gestations resulting from assisted-reproduction techniques, dramatically increase hospital charges. If all the multiple gestations resulting from assisted-reproduction techniques had been singleton pregnancies, the predicted savings to the health care delivery system in the study hospital alone would have been over $3 million per year. Although assisted reproduction provides tremendous benefits to families with infertility, the increased medical risks entailed by multiple-gestation pregnancies and the associated costs cannot be ignored. We suggest that more attention be paid to approaches to infertility that reduce the likelihood of multiple gestation.

Adolescent↗

PubMed1994

Complications of assisted reproductive techniques.

OBJECTIVE: To review and appreciate the relevant data on assisted reproduction techniques and their potential complications. DATA RESOURCES: Major publications on assisted reproduction that include the information concerning complications associated with this practice. RESULTS: Assisted reproduction is a common practice in modern reproductive medicine. Complications are associated with ovulation induction and the extracorporeal methods that are used for IVF-ET, GIFT, and zygote intrafallopian transfer (ZIFT). These complications are associated with laparoscopy, anesthesia, oocyte retrieval, and laboratory facilities. Pregnancies resulting from assisted reproduction are more complicated than spontaneous pregnancies. There are higher rates of ectopic, heterotopic, and multifetal pregnancies; abortions; and premature deliveries. Increased rates of perinatal mortality and morbidity result from prematurity, and higher rates of maternal diseases in pregnancy (preeclampsia, diabetes mellitus, bleeding, anemia) contribute to fetal intra-uterine growth restriction and maternal morbidity. CONCLUSIONS: Assisted reproduction practice should be well controlled in view of the potential for complications before and during pregnancies.

Embryo Transfer↗

PubMed2006

Developmental outcome of very low birth weight twins conceived by assisted reproduction techniques.

OBJECTIVE: To evaluate the differences in developmental outcomes between very low birth weight twins conceived by assisted reproduction techniques and those conceived spontaneously. STUDY DESIGN: Twenty-two sets of very low birth weight twins were evaluated by the Kyoto Scale for Psychological Development at 36 months of corrected age. Total developmental quotient and developmental quotient (DQ) for three subscales, posture-motor, cognition-adaptation and language-social, were evaluated. RESULTS: Twins conceived with medical assistance demonstrated a higher incidence of total DQ below 85 with lower DQ for cognition-adaptation and language-social skills than spontaneously conceived twins, whereas the quotient for posture-motor skills in medically assisted twins was comparable to that of spontaneously conceived twins. CONCLUSION: At 3 years of age very low birth weight twins conceived by assisted reproduction techniques demonstrated lower cognitive and language skills than twins conceived naturally.

Adult↗

PubMed2005

Safety of drugs used in assisted reproduction techniques.

Infertility may affect one in six couples; however, the development of the assisted reproduction technique (ART) created the opportunity for a large proportion of the infertile population to bear children. Pharmacological agents are routinely used in ART, and new ones are introduced regularly, with the aim of retrieving multiple oocytes to increase the prospect of pregnancy. The combinations of drugs that are used have specific adverse effects, but it is mostly the combined action of more than one agent that causes the greatest concern. The matter is complicated by the suspicion that some techniques in ART, for example intracytoplasmic sperm injection for severe male infertility problems (including azoospermia), may also contribute to the increase in adverse effects, especially congenital malformation. Gonadotropin releasing hormone (GnRH) agonists are widely used in controlled ovarian hyperstimulation. It may give rise to a short period of estradiol withdrawal symptoms and it may also lead to luteal phase deficiency. Similarly GnRHa antagonists, which have been recently introduced to control ovarian hyperstimulation, can lead to luteal phase deficiency and may cause some local injection site reactions. The more pure form of gonadotropin leads to less local injection site reactions and their main adverse effects are associated with the consequences of multiple ovulations. It has been proposed that gonadotropins may be a factor in the increasing risk of ovarian cancer and possibly breast cancer, but this has not been substantiated. Prion infection is another potential hazard, although no cases have been reported. Ovarian hyperstimulation syndrome is a well recognised complication of controlled ovarian hyperstimulation in ART. It is usually a result of recruitment of a large number of ovarian follicles. Efforts to minimise the incidence of this syndrome and its severity are now well developed. Congenital malformations are another possible adverse effect of fertility drugs, but it is more probable that the increase in congenital abnormality that is reported in ART is because of the population studied, i.e. patients already at high risk of congenital malformation, rather than the fertility drugs used or the technique employed. High order multiple pregnancy and its sequela is a well established complication of controlled ovarian hyperstimulation. This could be a result of multiple ovulations or more than one embryo replacement. Reducing the number of embryos transferred can reduce this more serious adverse effect for expectant mothers and for children conceived from ART.

Gonadotropins↗

PubMed2005

Effect of repeated assisted reproduction techniques on the ovarian response.

PURPOSE OF REVIEW: Despite the increasing success of assisted reproduction techniques, most couples need more than one cycle of controlled ovarian hyperstimulation to achieve a pregnancy. The effect of several cycles on the ovarian response in subsequent cycles is a concern for gynaecologists and patients. In addition, egg donors have the possible risk of an ovarian reserve decrease. In this review, we present published evidence on the effects of repeated assisted reproduction techniques on the ovarian response. RECENT FINDINGS: Recent available data indicate that ovarian response persists with subsequent cycles of controlled ovarian hyperstimulation in terms of oocytes being retrieved, although it is not clear whether an increased level of gonadotropins is required to achieve this response. There is a decrease in the number of oocytes retrieved in subsequent cycles due to increased female age as more cycles are needed. The oocytes retrieved in one cycle seem to come from the antral pool that otherwise would be atretic due to dominant follicle selection. SUMMARY: The mechanisms involved in the recruitment from atresia of more than one follicle are discussed and it is shown that repetitive ovarian stimulation does not appear to affect the ovarian reserve. Published evidence shows that gonadotropins alter the physiologic selection of one single dominant follicle but do not accelerate the recruitment of follicles from further cycles, confirming that there is no detrimental effect on ovarian function after repetitive controlled ovarian hyperstimulation.

Female↗

PubMed2003

Outcome of twin pregnancies after assisted reproductive techniques--a comparative study.

OBJECTIVE: To compare obstetrical and perinatal outcome of twin pregnancies after assisted reproductive techniques (ART) with that of twins conceived spontaneously. STUDY DESIGN: Hospital based retrospective study. RESULTS: There were 132 twin deliveries of which 36 were conceived after ART. Patients of the ART group were mostly nulliparous and slightly older. There was no statistically significant difference in the frequency of preterm delivery or mean gestational age at delivery. Elective Caesarean delivery was more frequent in twin pregnancies conceived after ART, and there were no other differences in maternal complications. There was also no difference in the mean birth weight or frequency of neonatal complication between the two groups. CONCLUSION: In this comparative study, the obstetric and neonatal outcomes between spontaneous twins and those conceived after ART are similar except for higher operative deliveries in the latter group of twins.

Adult↗

PubMed2006

Oxidative stress in an assisted reproductive techniques setting.

OBJECTIVE: The manipulation of gametes and embryos in an in vitro environment when performing assisted reproductive techniques (ART) carries the risk of exposure of these cells to supraphysiological levels of reactive oxygen species (ROS). The main objective of this review is to provide ART personnel with all the necessary information regarding the development of oxidative stress in an ART setting, as well as the sources of ROS and the mechanisms of oxidative stress-induced damage during ART procedures. The impact of oxidative stress on ART outcome and the different strategies designed to prevent it are also discussed. DESIGN: Review of international scientific literature. A question-and-answer format was adopted in an attempt to convey comprehensive information in a simple yet focused manner. RESULT(S): The pO(2) to which gametes and the embryo are normally exposed in vivo is significantly lower than in vitro. This results in increased production of ROS. Increase in levels of ROS without a concomitant rise in antioxidant defenses leads to oxidative stress. Lipid, protein, and DNA damage have all been associated with oxidative stress. This may ultimately result in suboptimal ART success rates. CONCLUSION(S): Many modifiable conditions exist in an ART setting that may aid in reducing the toxic effects of ROS.

Embryo, Mammalian↗

PubMed2002

Economic implications of assisted reproductive techniques: a systematic review.

BACKGROUND: Approximately one in six couples experiences problems with their fertility at some point in their reproductive lives. The economic implications of the use of assisted reproductive techniques require consideration. Herein, the health economics research in this area are critically appraised. METHODS: Multiple strategies were used to identify relevant studies. Each title and abstract was independently reviewed by two members of the study team and categorized according to perceived relevance. The selected papers were then assessed for quality and data were extracted, converted to UK pounds sterling at 1999/2000 prices, tabulated and critically appraised. RESULTS: A total of 2547 papers was identified through the searches; this resulted in 30 economic evaluations, 22 cost studies and five economic benefit studies that met the selection criteria. The quality of these studies was mixed; many failed to disaggregate costs, discount future costs or conduct sensitivity analyses. Consistent findings included the following: initiating treatment with intrauterine insemination appeared to be more cost-effective than IVF; vasectomy reversal appeared to be more cost-effective than ICSI; factors associated with poor prognosis decreased the cost-effectiveness of interventions. CONCLUSIONS: The cost-effectiveness of different interventions should be considered when making decisions about treatment. Future economic appraisals of assisted reproductive techniques would benefit from more robust methodology than is evident in much of the published literature to date.

Adult↗

PubMed1992

Outcome of 143 pregnancies conceived by assisted reproductive techniques.

One hundred and forty-three pregnancies conceived by assisted reproductive techniques (ART) from October 1985 to June 1989 in the National University Hospital, Singapore, resulted in 66 deliveries and 89 babies. There were 27 (18.7%) biochemical pregnancies, 44 (30.7%) clinical miscarriages and 6 (4.2%) ectopic pregnancies when total pregnancies were considered. Of those who continued pregnancy to second trimester multiple births occurred in 20 (13.3%) patients. A high incidence of vaginal bleeding and hypertension in pregnancy was noted in 32 (48.5%) patients and 18 (27.3%) patients, respectively. Caesarean section was the method of delivery in 48.5% of patients. Twenty-six (29.2%) babies required admission to the neonatal intensive care unit. All babies except one set of twins delivered at 24 weeks of amenorrhoea survived. Fetal abnormality was noted in 2 cases.

Adult↗

PubMedDate not supplied

Assisted reproduction techniques.

Many couples with infertility will require a form of assisted reproduction to achieve a pregnancy. Assisted reproduction techniques, including intrauterine insemination, gamete intrafallopian transfer and in-vitro fertilisation, are considered in this review.

Female↗

PubMed2006

Reduced aromatase activity in granulosa cells of women with endometriosis undergoing assisted reproduction techniques.

The aim of the present study was to measure the in vitro aromatase activity in granulosa cells of women with endometriosis submitted to assisted reproduction techniques. A case-control study was conducted on eight patients with endometriosis and eight with other infertility causes submitted to in vitro fertilization or intracytoplasmic sperm injection. Granulosa cells were obtained from pre-ovulatory follicles during oocyte retrieval and cultured for 24 h in the presence or absence of testosterone (2 x 10(-6) and 2 x 10(-5) M), follicle-stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) (both at 50 ng/ml). Estradiol (radioimmunoassay) was measured in the obtained culture fluids. The basal production of estradiol and its production under testosterone addition to the culture (aromatase activity) were analyzed. Reduced aromatase activity was detected in cultured granulosa cells in endometriosis cases, compared with controls, when testosterone was added at the concentration at 2 x 10(-6) M (p = 0.0303). The basal production of estradiol was also reduced in endometriosis patients (p = 0.0390). The effect of addition of FSH and IGF-I did not differ between groups. In conclusion, the in vitro basal production of estradiol and aromatase activity in granulosa cells were reduced in women with endometriosis submitted to assisted reproduction techniques, compared with the control group.

Adult↗

PubMed2000

Evaluating strategies for improving ovarian response of the poor responder undergoing assisted reproductive techniques.

OBJECTIVE: To assess the efficacy of various controlled ovarian hyperstimulation (COH) regimens in the prior poor-responder patient preparing for assisted reproductive techniques. DESIGN: English-language literature review. PATIENT(S): Candidates for assisted reproductive techniques who had been defined as having a prior suboptimal response to standard COH regimens. INTERVENTION(S): A variety of regimes are reviewed, including increased gonadotropin doses, change of gonadotropins, adjunctive growth hormone (GH), luteal phase (long) GnRH agonist (GnRH-a) initiation, early follicular phase (flare) GnRH-a initiation, low-dose luteal phase (ultrashort) GnRH-a initiation, progestin pretreatment, and microdose flare GnRH-a initiation. MAIN OUTCOME MEASURE(S): Maximal serum E(2) levels, follicular development, dose, and duration of gonadotropin therapy, cycle cancellation rates, oocytes retrieved, embryos transferred, and clinical and ongoing pregnancy rates. RESULT(S): A lack of uniformity in definition of the poor responder and of prospective randomized trials make data interpretation somewhat difficult. Of the varied strategies proposed, those that seem to be more uniformly beneficial are microdose GnRH-a flare and late luteal phase initiation of a short course of low-dose GnRH-a discontinued before COH. CONCLUSION(S): No single regimen will benefit all poor responders. General acceptance of uniform definitions and performance of large-scale prospective randomized trials are critical. Development of a reliable precycle screen will allow effective differentiation among normal responders, poor responders, and those who will not conceive with their own oocytes.

Clinical Protocols↗

PubMed2005

Screening of mutations in the CFTR gene in 1195 couples entering assisted reproduction technique programs.

Genetic testing of the cystic fibrosis transmembrane conductance (CFTR) gene is currently performed in couples undergoing assisted reproduction techniques (ART), because of the high prevalence of healthy carriers in the population and the pathogenic relationship with congenital bilateral absence of vas deferens (CBAVD). However, discordant data have been reported concerning the usefulness of this genetic test in couples with no family history of cystic fibrosis (CF). In this study, we report the results of CFTR molecular screening in 1195 couples entering ART. Genetic testing was initially carried out in a single partner of each couple. CFTR mutations were detected in 55 subjects (4.6%), a percentage that overlaps with the one reported in the general population. However, significantly higher frequencies of were found in CBAVD individuals (37.5%) and in males with nonobstructive azoospermia (6.6%). The 5T allele was found in 78 patients (6.5%). This figure was again significantly different in males with nonobstructive-azoospermia (9.9%) and in those with CBAVD (100%). All together, 139 subjects (11.6%) had either a CFTR mutation or the 5T allele. Subsequent molecular analysis of their partners disclosed a CFTR mutation or 5T allele in nine cases (6.5%). However, none of these couples had CFTR alterations in both members, a CFTR mutation being invariably present in one partner and the 5T allele in the other. In order to improve genetic counselling of these couples, the TG-M470V-5T association was analyzed, and a statistically significant relationship between 12TG-V470 and CBAVD was detected.

Alleles↗

PubMed2003

Male age is not an independent factor to affect the outcome of assisted reproductive techniques.

Controversy exists whether advanced male age is associated with poor sperm quality and subsequent failure in the assisted reproductive techniques (ART). The purpose of this study was to evaluate the effect of male age on sperm quality and the outcome of ART as well as the association of male age with other relevant factors, particularly with the female age. A retrospective study was performed in order to evaluate the effect of male age on the sperm parameters in 880 routine seminal analyses. Additionally, sperm parameters were also compared among different age groups in 919 cases with male factor infertility who had been included in an ART programme. The laboratory and clinical results of ART (fertilization rate, number and quality of embryos transferred, as well as pregnancy rates) were compared according to different age groups. The results were also evaluated by one-way correlation and also step-wise logistic regression analysis to identify the interactions and correlations between different parameters. There were no statistically significant differences between male age groups in terms of sperm concentration, motility and morphology either in routine seminal analyses or in ART groups. In the ART group, a statistically significant linear correlation was present between male and female ages. Male age was increasing in parallel to female age. Female age was also correlated significantly with ART results. In one-way correlation analysis, male age was found to be correlated with the pregnancy rate, but not with fertilization rate and the quality of the transferred embryos. However, regression analysis revealed that correlation between male age and pregnancy results was simply dependent on the effect of the female age. Seminal parameters did not reveal a significant change with the increasing male age. The effect of male age on ART results in cases with male factor infertility is not a direct effect but a reflection of the negative impact of the parallel increase in the female age.

Adult↗

PubMed2006

Successful pregnancy achieved by assisted reproductive techniques in a woman with severe congenital bicuspid aortic valve stenosis.

OBJECTIVES: To report a twin pregnancy achieved by assisted reproductive techniques in a woman with severe congenital bicuspid aortic valve stenosis. METHODS: Intracytoplasmic sperm injection and embryo transfer was performed in a 38-year-old woman with a complaint of infertility for 8 years due to male factor and who previously had the diagnosis of severe congenital bicuspid aortic stenosis. Clinical and echocardiography follow-up during pregnancy was done. RESULTS: The woman had severe congenital aortic stenosis with a valve area of 0.4 cm(2) and a peak gradient of 57 mmHg. In the first trial, twin pregnancy was achieved. She had an uneventful course of pregnancy in terms of cardiac functions. She underwent caesarean section at 36 weeks of gestation and had a healthy female and a male newborns. CONCLUSIONS: A woman with a severe congenital bicuspid aortic valve may get pregnant and deliver healthy newborns with intensive prenatal care and follow-up. The severe congenital bicuspid aortic valve stenosis may not be considered an absolute contraindication for assisted reproductive techniques and pregnancy.

Adult↗

PubMed1999

Sexually-transmitted diseases and assisted reproduction techniques.

As to the correlation between sexually transmitted diseases (STD) and assisted reproduction techniques (ART) we must consider that it is necessary to collate information and start screening campaigns for all sexually active individuals with the purpose of prevention and early diagnosis of STD which may cause of sterility. Before starting any kind of ART it is mandatory to perform diagnostic tests in all couples and to apply the correct therapy for any STD: treatment must always involve both partners and results must be carefully checked. All diagnostic examinations and all ART procedures should not carry the risk of transmitting any infection. When one or both of the partners are carriers of a transmissible infection (especially AIDS) it is advisable to negate ART or to start treatment, particularly for the semen, in order to reduce the level of infection and to avoid the transmission of any infection to the fetus.

Acquired Immunodeficiency Syndrome↗

PubMed1993

A critical appraisal of assisted reproduction techniques.

Several treatments for infertility have been promoted with only little supporting objective data demonstrating their therapeutic value. The choice of an assisted reproductive technique depends on a balance between numerous factors. Seldom is the choice absolute as in patients with tubal block. There is conflicting evidence on the efficacy of simpler methods such as ovarian stimulation with or without artificial insemination and the available data suggest that the more invasive methods such as gamete intra-Fallopian transfer or in-vitro fertilization are more effective in the treatment of couples with unexplained infertility. Equally, there is no conclusive evidence that pregnancy rates with any of the invasive techniques are superior to any others. However, a higher implantation rate following tubal embryo transfers is observed in many studies. This review presents a critical assessment of the effectiveness of assisted reproductive techniques.

Embryo Transfer↗

PubMed2004

Gonadotropin-releasing hormone antagonists for assisted reproductive techniques: are there clinical differences between agents?

Gonadotropin-releasing hormone (GnRH) antagonists have been tested extensively in ovarian stimulation protocols for assisted reproductive techniques (ART). GnRH antagonists immediately and rapidly inhibit gonadotropin release by the anterior pituitary gland by competitive blockage of the GnRH receptor, preventing and interrupting luteinising hormone surges in controlled ovarian hyperstimulation for infertility treatment. A review of the available literature on GnRH antagonists for ART is presented, focusing on the pharmacological and clinical properties of the two compounds available on the market, cetrorelix and ganirelix. Both cetrorelix and ganirelix are well tolerated and effective drugs for controlled ovarian hyperstimulation and are of comparable value for infertility treatment. Cetrorelix is available as a 0.25mg preparation for daily injections and as a 3mg intermediate depot preparation. Ganirelix is available as a 0.25mg preparation for daily injections.Currently, two treatment protocols are used in clinical practice: the GnRH antagonist multiple-dose protocol and the GnRH antagonist single-dose protocol. Both protocols are effective and well tolerated. Cetrorelix and ganirelix have not yet been directly compared in a clinical trial; nor have the single-dose and the multiple-dose approaches been compared in a randomised, controlled trial. Data to compare these compounds in clinical terms can be extrapolated only from results of phase II dose-finding studies and phase III studies comparing GnRH agonist cycles with GnRH antagonists in single- and multiple-dose protocols. Therefore, all conclusions on clinical differences between cetrorelix and ganirelix should remain tentative, as they are based on a limited amount of available data.Randomised, controlled trials comparing cetrorelix and ganirelix are warranted to further evaluate benefits and drawbacks of individual GnRH antagonists. Furthermore, more data are needed to determine the efficacy and safety of cetrorelix and ganirelix in established treatment protocols in patients other than those included in clinical trials investigating new drugs, such as "poor responders", patients with polycystic ovaries, patients with a history of allergy or overweight patients.

Clinical Trials as Topic↗