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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↗

[In vitro fertilization laboratory. Clinical features of assisted reproduction techniques. Male infertility treatment in a reproduction medicine centre].

The development of fertilization techniques such as ICSI, complementary to conventional in vitro fertilization, have been a great advance in the treatment of the male factor. ICSI with spermatozoa from ejaculate allows successful treatment of severe male factor, patients with previous failures of fertilization, and also cases without apparent cause. ICSI with spermatozoa obtained directly from the testicle allows couples in which the male suffers azoospermia, either obstructive or secretory, achieving pregnancy. After ICSI, pregnancy rates are similar to the ones after conventional in vitro fertilization. It is necessary to evaluate the genetic risk for children born after ICSI. On the one hand there are anomalies bound to subfertile population they come from, on the other chromosome anomalies generated de novo. ICSI does not increase the incidence of major malformations. It is recommendable to perform prenatal diagnosis in pregnancies obtained by ICSI.

Chromosome Aberrations↗

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↗

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↗

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↗

A comparative analysis of second-trimester ultrasound dating formulae in pregnancies conceived with artificial reproductive techniques.

A dataset of 64 pregnancies conceived by artificial reproductive techniques was studied to assess the accuracy of second-trimester dating formulae when these were applied in routine ultrasound clinics in different centers. Dating formulae for biparietal diameter (BPD) and femur length (FL) were derived for a gestational age range of 14-23 weeks. The best fit curves represented linear equations: gestational age (days) = 44.2 + 2 x BPD; and gestational age (days) = 67.4 + 2.3 x FL. Twelve published formulae for biparietal diameter and femur length were reviewed and systematic and random errors were calculated for these formulae when they were applied to second-trimester scan measurements in precisely dated pregnancies. Overall, published dating formulae performed well in predicting gestational age. The 95% confidence interval was 8.3 days for biparietal diameter and 10.2 days for femur length. The study confirms the accuracy of ultrasound dating in routine ultrasound clinics and supports the use of ultrasound measurement alone in preference to menstrual history for dating pregnancy.

Anthropometry↗

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↗

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↗

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↗

Advanced reproductive techniques in goats.

The use of ultrasonography for pregnancy diagnosis and reproductive tract evaluation in the goat has become more common in the past decade. Pregnancy-specific hormone assays are commercially available for pregnancy determination in goats. Hormonal methods of synchronization of estrus for artificial insemination have been refined, but a number of factors still make pregnancy results variable. Caprine embryo transfer is widely used commercially. More advanced reproductive techniques such as in-vitro production of embryos and cloning have been accomplished in goats; success rates with these techniques will likely rapidly improve.

Animal Husbandry↗

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↗

[Are French results in assisted reproductive techniques so bad?].

OBJECTIVE: Comparative analysis of French results in Assisted Reproductive Techniques (ART) versus those from other European countries and the United States. POPULATION AND METHODS: The study was achieved by using the officially available data. The analysis was faced with a lot of difficulties in relation with the various methods of collecting data in the different countries. RESULTS: Nevertheless, it appears clearly that French results are among the lowest in Europe with a 22% rate for pregnancy per ovum pick-up with IVF and 23.4% with ICSI, when most of the other countries report rates that are close to or over 30%. Neither the patients' pick-up recruitment nor specific practices of ART can explain this difference that certainly comes from a deficient quality of the French IVF centres. DISCUSSION AND CONCLUSION: We think that four main end-points can explain this situation: the lack of financial support, the lack of human force, the lack of transparency and finally the opposition between clinician and biologist that has blocked the set-up of integrated ART centres, and probably a poor quality culture.

Adult↗

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↗

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↗

[Indications and modalities of assisted reproductive techniques in infertile women with cystic fibrosis].

OBJECTIVE: To treat cystic fibrosis women who failed to conceive. PATIENTS AND METHODS: Multidisciplinary coordinated approach in 20 infertile women affected with cystic fibrosis. Advisability of pregnancy was based on the assessment of pulmonary and nutritional status, risks of maternal health deterioration, infertility factors, risk of cystic fibrosis in the offspring. Assisted reproductive techniques in moderately affected women are described. RESULTS: Three patients requested only information, three were discouraged, two are still evaluated, 12 were treated and three delivered healthy children. The pulmonary status of each patient remained unchanged 36 months after delivery, and all three children remain healthy. DISCUSSION AND CONCLUSION: Assisted reproductive techniques are an option in moderately affected infertile cystic fibrosis women. Advisability and management of pregnancy should be provided by a coordinated team of healthcare professionals with knowledge and experience in cystic fibrosis.

Adult↗

Psychological evaluation test after the use of assisted reproduction techniques.

PURPOSE: The emotional changes provoked by the use of assisted reproduction techniques (ART) may trigger important psychological reactions. The objective of the present study was to develop a psychological evaluation test (PET-ART) in order to identify the occurrence of psychological problems and to facilitate their treatment. METHODS: A total of 128 women were submitted to PET-ART of the Center for Human Reproduction, "Sinhá Junqueira" Maternity Foundation, after application of IVF/ICSI program at least once. The causes of infertility were male-related in 45% of cases, female-related in 48%, and both male- and female-related in 7%. Infertility was primary in 79% of cases and secondary in 21%. The mean age of the women was 34.5 +/- 5.2 years and the mean age of the men was 37.9 +/- 6.8 years. The PET-ART was evaluated using a questionnaire with 15 questions selected in order to detect emotional reactions caused by infertility. The responses were assigned four grades with respect to intensity (1 = mild intensity; 2 = medium intensity; 3 = high intensity; and 4 = maximum or unbearable intensity). The sum of the responses corresponded to PET-ART score ranging from 15 to 60 points. The reliability of the questionnaire was evaluated by the alpha coefficient of Cronbach. RESULTS: The PET-ART identified five questions receiving 50% or more responses of the high/maximum intensity type (sum of the percentages of responses with a score of 3 and 4). The questions were the following: 1--The waiting time before being submitted to a pregnancy test (82.8% of the patients); 2--A negative result of the pregnancy test (77.3% of the patients); 3--The degree of anxiety in a new attempt to obtain pregnancy (76.5% of the patients); 4--Finding the money necessary for the repetition of the IVF/ICSI techniques (66.4% of the patients); 5--The possibility of collecting few eggs, or of forming or not an embryo in the laboratory is an expectation that makes me anxious (57.8% of the patients). The mean PET-ART was 33 +/- 6. The alpha coefficient of Cronbach was 0.757. CONCLUSIONS: The PET-ART was an efficient tool for the identification of women with emotional changes provoked by the application of ART and for the planning of their treatment. However, a general psychological approach was developed for each emotional factor regardless of PET-ART.

Adult↗

[Andrologic indications for assisted reproduction techniques. When can increased fertilization rates by assisted reproduction be expected?].

Basics: When the cause of a sterile marriage must be assumed to lie with the husband, attempts are often made to resolve the problem by applying the techniques of assisted reproduction, viz insemination and in vitro fertilization (IVF). In such a case, this is the treatment of the wife, who may herself be completely healthy. Major points: In the case of oligoasthenoteratozoospermia (OAT) syndrome, the various techniques available are unable to decisively increase the conception rate. In particular, all IVF working groups are agreed that successes are greatly reduced in the case of inferior sperm quality, as compared with other indications. The "poorer" the original findings, the lower are the fertilization rates. The costs of IVF of about DM 6,000 per cycle mean that, with a success rate of some 8%, the overall cost for each pregnancy is about DM 72,000. This fact tends not to receive sufficient mention in discussions with the married couple. So far, it has not been possible to predict the success rate of an IVF on the basis of an examination of the ejaculate with any degree of accuracy with the aid of the parameters sperm cell density, motility and morphology. Nor do biological tests or an investigation of acrosome function help improve the situation. Even the direct observation of the fertilization of a human ovum, is of questionable value.(ABSTRACT TRUNCATED AT 250 WORDS)

Fertilization in Vitro↗