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Immunoglobulins and cytokines level in follicular fluid in relation to etiology of infertility and their relevance to IVF outcome.

OBJECTIVE: The aims of the present study were to (i) determine the presence and concentration of albumin fractions (alpha1, alpha2, beta, gamma), immunoglobulins (IgA, IgG, IgM) and cytokines [interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF)] in periovulatory ovarian follicular fluid (FF) of in vitro fertilization (IVF) patients, (ii) examine the relationship between these parameters and the etiology of infertility as well as the IVF outcome and (iii) find out if these parameters in FF could be used as a predictive factor of IVF outcome. DESIGN: The levels of albumin fractions, immunoglobulin and cytokines were measured from women who underwent IVF therapy for various indications and the results were compared between the patient groups and IVF outcome. MATERIALS AND METHODS: Follicular fluid was obtained from 160 IVF patients. A total of 79 patients underwent controlled ovarian hyperstimulations (COH) either with follicle-stimulating hormone (FSH) or HMG. Whereas, the HMG was used for the second set of patients (n=81) - after down regulation with gondotropin-releasing hormone agonists (Gn-RHa) - the protein fractions were determined using electrophoresis separation. Immunoglobulins were measured using a commercial kits and the concentration of cytokines was determined by the highly sensitive enzyme-linked immunosorbent assay (ELISA) methods. RESULTS: The stimulation regimens used have no effect on albumin (alpha1, alpha2, beta, gamma) and immunoglobulin (IgA, IgG, IgM) concentrations, as no significant difference was observed between the two groups. Besides, no specific relationship was found between the concentration of these investigated parameter in FF and etiology of infertility or fertilization, cleavage and pregnancy rate. Besides, there were no significant differences between the groups for any cytokine investigated. Moreover, there were no correlations between the concentration of IL-6, IL-8 and GM-CSF in FF and steroid hormone concentration in the blood at the day of oocytes retrieval or IVF outcome. IN CONCLUSION: Total protein, albumin fraction, immunoglobulins and cytokines level in FF of patients undergoing COH for IVF therapy for various etiology of infertility could not be a useful parameter for predicting IVF outcome.

Adult↗

Congenital malformations in 4224 children conceived after IVF.

BACKGROUND: The percentage of children born after IVF will continue to increase due to demographic changes such as increasing maternal age and new developments in assisted reproduction techniques. IVF conceptions may carry an increased risk of congenital malformations. METHODS: We compared overall and specific congenital malformation rates calculated for IVF children (n = 4224) and naturally conceived children (n = 314 605), using records from the same Dutch national database for the years 1995 and 1996 and controlling for confounding maternal factors. RESULTS: The overall crude odds ratio (OR) for the risk of any malformation for IVF children compared with naturally conceived children was 1.20 [95% confidence interval (CI): 1.01-1.43]. After correction for differences in maternal age, parity and ethnicity between the IVF and control population the OR was 1.03 (95% CI: 0.86-1.23). The crude OR for IVF children appeared higher for the cardiovascular organ system and for several specific minor congenital malformations. However, these could be chance findings due to comparison of many malformation categories or may result from remaining differences in ascertaining malformations between IVF and naturally conceived children. CONCLUSIONS: The small increase in overall congenital malformations observed in the IVF children appears to be attributable to differences in maternal characteristics and not to any aspect of the IVF procedure.

Adult↗

Developmental outcome at 2 years of age for children born after ICSI compared with children born after IVF.

BACKGROUND: Since the introduction of ICSI in 1991, medical outcome studies on ICSI children have been performed, but few have addressed developmental outcome. Hence, this outcome was assessed by performing a standard developmental test on children born after ICSI as compared with children born after IVF, at the age of 2 years. METHODS: In a prospective study, the medical and developmental outcome of 439 children born after ICSI (378 singletons, 61 twins) were compared with those of 207 children born after IVF (138 singletons, 69 twins), at the age of 24-28 months. These children were part of a cohort of children followed since birth. Of children reaching the age of 24-28 months between May 1995 and March 2002, 44.3% (2375/5356) were examined by a paediatrician who was unaware of the type of treatment used for each couple. Of all the children born, 12.2% (439/3618) in the ICSI group and 11.9% (207/1738) in the IVF group underwent a formal developmental assessment using the Bayley Scale of Infant Development (mental scale) by a paediatrician blinded to the type of treatment. RESULTS: There was no significant difference in maternal educational level, maternal age, gestational age, parity, birthweight, neonatal complication rate or malformation rate at 2 years between ICSI and IVF singletons, or between ICSI and IVF twins. No significant difference was observed in the developmental outcome using the Bayley scale at the age of 24-28 months (raw scores or test age) between ICSI children or IVF children. A multivariate regression analysis for the singleton children indicated that parity, sex (boys had lower scores than girls) and age had a significant influence on the test result, but that the fertility procedure (ICSI versus IVF) did not influence the test result. ICSI children from fathers with low sperm concentration, low sperm motility or poor morphology had a similar developmental outcome to that of children from fathers with normal sperm parameters. There were no significant differences between the initial cohort and the group lost to follow-up, nor between the psychologically tested and the non-tested group for a number of variables such as maternal educational level, birthweight in singletons and neonatal malformation rate. Although only some of the cohort of ICSI children were evaluated, a representative sample of both ICSI and IVF children was compared. CONCLUSIONS: There is no indication that ICSI children have a lower psychomotor development than IVF children. Paternal risk factors associated with male-factor infertility were found not to play a role in developmental outcome.

Aging↗

Risk of benign gynaecological diseases and hormonal disorders according to responsiveness to ovarian stimulation in IVF: a follow-up study of 8714 women.

BACKGROUND: Over the past decade, attention has been focused increasingly on the long-term health effects of IVF in women. Assuming that hormonal changes due to stimulation regimens for IVF are strongest among 'high' responders, we evaluated whether responsiveness to ovarian stimulation in IVF is predictive of the risk of benign gynaecological disorders >12 months after the last IVF cycle. METHODS: A nationwide historical cohort study of women who underwent IVF treatment was conducted. After a median time of 4.6 years following the last IVF treatment cycle, 8714 cohort members completed a health survey questionnaire that inquired about reproductive variables and the occurrence and age at onset of specific medical conditions including uterine leiomyoma, surgically removed ovarian cysts and thyroid disorders. Detailed data on cause of subfertility and IVF treatment were collected from the medical records. Women were included in the 'high responders' group when on average >/=14 oocytes were retrieved per IVF cycle (n = 1562), in the 'normal responders' group when they had a mean number of 4-13 retrieved oocytes (n = 6033), and in the 'low responders' group when they had a mean number of 0-3 retrieved oocytes per cycle (n = 1119). RESULTS: Among women with a high response to ovarian stimulation, we found a borderline significantly decreased risk of uterine leiomyoma [relative risk (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0] and surgically removed ovarian cysts (RR = 0.6; 95% CI 0.3-1.0) in comparison with 'normal responders'. After OHSS, the age-adjusted RRs were 1.8 (95% CI 0.9-3.8) for having surgically removed ovarian cysts and 1.0 (95% CI 0.4-2.2) for uterine leiomyoma (both not significant). CONCLUSIONS: Despite the small number of events observed, highly elevated risks of gynaecological disorders and hormonal diseases in women undergoing IVF treatment can be excluded based on the present data and this follow-up period. Women with a low response to ovarian stimulation tended to have higher risks of benign gynaecological diseases than high responders.

Cohort Studies↗

A postal survey of hydrosalpinx management prior to IVF in the United Kingdom.

BACKGROUND: In the last decade, numerous studies have demonstrated concern about the presence of hydrosalpinx and its management in patients undergoing IVF. We evaluated the current management of hydrosalpinx prior to IVF treatment in the UK. METHODS: A total of 117 postal survey, anonymous, sealed questionnaires were sent to all IVF centres in the UK, to determine the policy for the management of hydrosalpinx in infertile women prior to IVF treatment. RESULTS: There were 88 (75%) responders, of which 80 (91%) indicated that they discussed the effect of hydrosalpinx on IVF outcome. Ten (12%) units did not recommend treatment of hydrosalpinx prior to IVF treatment, while 30 (36%), 27 (33%) and 16 (19%) recommended treatment weakly, strongly and very strongly respectively. The treatment options offered by clinicians were laparoscopic salpingectomy (75%), open salpingectomy (45%), salpingostomy (40%), proximal tubal occlusion (34%), transvaginal songraphic (TVS) aspiration during oocyte collection (23%) and TVS aspiration before oocyte collection (10%). The frequency of use varied from one option of treatment to another. Only 28% of the responders had a protocol or guidelines for the management of hydrosalpinx. CONCLUSIONS: More attention should be given to patients with hydrosalpinx prior to IVF treatment and patients should be counselled about the negative effect of hydrosalpinx on IVF outcome. There is a wide variation in the management of hydrosalpinx prior to IVF treatment in the UK and many treatment options may be questionable, as they are not yet based on evidence.

Ambulatory Care Facilities↗

Legal issues in IVF.

It is desirable when considering legal issues related to IVF not to restrict attention solely to the impact of laws in existence at the time the IVF technology appeared. Laws then in existence were not designed with IVF in mind. New laws are needed, particularly to deal with legal problems that will arise from 'existing' laws in relation to two unprecedented features of IVF. These are the new technology whereby fertilized human eggs may be frozen, stored and later used for childbearing, and the fact that a 'host' mother may bear an IVF embryo. This chapter has discussed legal issues in IVF by examining in succession: a number of matters of basic social concern that require attention and raise questions that should be answered before new laws are made the need for laws on IVF to rest on clear principles acceptable to the community the application to IVF of 'existing' laws in six countries (France, the United States, Canada, England, Israel and Australia) and the kinds of problem that are thereby raised new laws that have already been created in Australia specifically to regulate IVF, and new laws that are in the course of preparation in the United Kingdom.

Australia↗

Effects of myomas or prior myomectomy on in vitro fertilization (IVF) performance.

OBJECTIVE: The purpose of this study was to determine the effect of the presence of myomas and prior myomectomy on the pregnancy rate and pregnancy outcome in an in vitro fertilization (IVF) program. DESIGN: Data collected from office and hospital records were analyzed retrospectively. SETTING: Patients (all with private insurance carriers) were enrolled in an academic IVF program at The Jones Institute for Reproductive Medicine. PATIENTS: All IVF patients enrolled in series 26-41, from 1987 to 1990, were reviewed. Only patients with well-documented myomas [by laparoscopy, laparotomy, hysteroscopy, or hysterosalpingography (HSG)] or prior myomectomy (confirmed by operative and pathology report) were included. MAIN OUTCOME MEASURES: Pregnancy rates and pregnancy outcome were the main outcome measures. Pregnancy rates were calculated per preovulatory embryo transfer. Chi-square, Student t-test, and the Whitney-Mann test were used in the statistical analysis and P less than 0.05 was considered significant. RESULTS: Among 1415 IVF patients, 11 had confirmed myomas present and 47 others had prior myomectomies. The mean age of patients with myomas and myomectomy was 37.1 +/- 4.1 and 36.1 +/- 1.9 years, respectively. Ten of the patients with myoma had normal endometrial cavities on HSG. Subserosal tumors were present in 10 of 11 patients with myomas. Ten of the 47 myomectomy patients had an abnormal cavity prior to surgery and all were corrected. About half of the patients with prior myomectomy had subserous myomas, while 10% were submucous in location. Two of the patients had hysteroscopic removal; all the rest were performed abdominally. The ongoing pregnancy rate from fresh embryo transfer for patients with myomas and myomectomy was 20.8 and 16.9%, respectively. This was comparable to the 19.0% ongoing pregnancy rate for all patients in these series. Despite the small number, and the fact that most had subserosal myomas, patients with myomas had a 50% abortion rate, while those postmyomectomy had a 34.2% abortion rate (statistically not significant). Moreover, if subdivided by their primary IVF indications, patients with prior myomectomy had similar ongoing pregnancy rates from fresh embryo transfer compared to the whole IVF population. CONCLUSION: The incidence of myomas or prior myomectomy among infertility patients presenting for IVF was rather low. Myomectomy did not interfere with IVF performance in relation to overall and ongoing pregnancy rate.

Female↗

Comparison of G1.2/G2.2 and Sydney IVF cleavage/blastocyst sequential media for the culture of human embryos: a prospective, randomized, comparative study.

OBJECTIVE: To compare two commercially available sequential media, G1.2/G2.2 and Sydney IVF cleavage/blastocyst media, as supports for human embryo culture. DESIGN: Prospective randomized study. SETTING: University-based IVF clinic. PATIENT(S): Two hundred forty-nine patients undergoing IVF treatment for the first or second time, randomly allocated at the time of oocyte retrieval, to either culture in G1.2/G2.2 or Sydney IVF media. INTERVENTION(S): Oocyte recovery, IVF or intracytoplasmic sperm injection, embryo culture, transfer on day 3 or day 5/6. MAIN OUTCOME MEASURE(S): Developmental stage on day 3, blastocyst rate, pregnancy outcome as assessed by beta hCG positive test, implantation rates, and ongoing pregnancies. RESULT(S): Embryos cultured in G1.2/G2.2 media displayed a faster kinetics of cleavage, compaction, blastulation, and hatching, but a lower day 3 embryo quality than those grown in Sydney IVF media. For patients with at least five embryos, G1.2/G2.2 media yielded higher implantation rates (26.2%) in our day 3 embryo transfer program when compared to Sydney IVF medium (15.5%), whereas similar implantation rates were obtained for day 5/6 embryo transfer for both media (43.1% and 36.1%, respectively). CONCLUSION(S): In our day 3 embryo transfer program, G1.2/G2.2 media were superior to Sydney IVF media, whereas both media yielded similar outcomes in our blastocyst transfer program.

Adult↗

Pronuclear stage cryopreservation after intracytoplasmic sperm injection and conventional IVF: implications for timing of the freeze.

OBJECTIVE: To compare clinical outcomes of frozen embryo transfers using cryopreserved pronuclear stage oocytes that had undergone either intracytoplasmic sperm injection (ICSI) or conventional IVF. DESIGN: Observational. SETTING: A tertiary referral reproductive medicine unit. PATIENT(S): Couples undergoing either ICSI or conventional IVF from January 1, 1995 to December 31, 1997. INTERVENTION(S): Patients underwent a standard controlled ovarian hyperstimulation protocol and transvaginal ultrasound-guided oocyte retrieval. All normally fertilized (2PN) oocytes exceeding a specified embryo number designated for fresh transfer were immediately cryopreserved at the pronuclear stage. Our cryopreservation method included timing of the freeze according to pronuclear morphology. Subsequent frozen embryo thaw-transfer cycles were usually performed by thawing only the intended number of embryos for transfer. MAIN OUTCOME MEASURE(S): Thaw survival rate, implantation rate, clinical pregnancy rate, delivery rate. RESULT(S): Ninety-six thaw-transfer cycles (n = 72) and 93 thaw-transfer cycles (n = 67) were undertaken in patients who had previously undergone conventional IVF or ICSI, respectively. Embryo thaw survival rates (IVF, 90.4%; ICSI, 91.1%) were similar. Clinical pregnancy (IVF, 40.6%; ICSI, 44.1%) and delivery (IVF, 36.4%; ICSI, 39.8%) rates per transfer, as well as implantation (IVF, 19.1%; ICSI, 19.9%) rates, were also similar. There were only four clinical pregnancy losses in both groups. CONCLUSION(S): Embryo thaw survival is similar for cryopreserved pronuclear stage oocytes derived from ICSI and conventional IVF. Clinical pregnancy, implantation and delivery rates were also similar for the two groups. In addition, there was no increase in the rate of pregnancy loss in ICSI patients after frozen embryo transfers.

Adult↗

Eight years' experience with an IVF surrogate gestational pregnancy programme.

The aim of this study was to retrospectively audit eight years' experience of an IVF surrogate gestational programme and to compare the outcome of surrogacy due to absence of the uterus with surrogacy indicated for repeated IVF failure and recurrent abortions. A total of 60 cycles of IVF surrogate pregnancy were initiated in 19 treated couples. Absence of the uterus was the indication for surrogacy in 10 cases: Rokitansky syndrome (eight cases) and post-hysterectomy (two cases) designated as group A. The indications in the remaining nine patients (group B) were: IVF implantation failure (three cases), habitual abortions (four cases) and deteriorating maternal diseases (two cases). IVF performance and subsequent pregnancy outcome of groups A and B were compared. There was no difference in ovarian stimulation parameters and in IVF performance between the groups A and B. The overall pregnancy rate per transfer was 10/60 (17%). The pregnancy rates per patient and per transfer were 7/10 (70%) and 7/35 (20%) in group A compared with 3/9 (33%) and 3/25 (12%) in group B. A median number of three treatment cycles were needed to achieve pregnancy. In conclusion, the existence or absence of the uterus in the commissioning mothers is irrelevant for their IVF performance and conception rates. In patients who conceived after more than three IVF cycles, an additional 'oocyte factor' might be present.

Abortion, Habitual↗

Sibling oocyte submission to IVF and ICSI in unexplained infertility patients: a potential assay for gamete quality.

In order to reduce total fertilization failure in unexplained infertility, sibling oocytes were submitted to both conventional IVF and intracytoplasmic sperm injection (ICSI). Two groups of ICSI embryos were compared in unexplained infertility patients: those derived from ICSI when IVF had failed to fertilize, and those derived from ICSI while their sibling oocytes were fertilized by IVF. The outcome of oocytes fertilized exclusively by ICSI (essential ICSI, n = 749) was compared with those fertilized both by IVF and ICSI (non-essential ICSI, n = 957) in all IVF patients treated for unexplained infertility at the Hadassah Hospital (1999-2002). The latter group was further subdivided into ICSI and IVF embryos. Total fertilization rate was 54%. Fertilization rates by ICSI were lower in the essential ICSI compared with the non-essential ICSI group, at 65 and 73% (P < 0.025). Pregnancy rates per embryo transfer in the essential ICSI group (49%), ICSI derived embryos group (55%) and IVF derived embryos (44%) from the non-essential ICSI group, were similar. Implantation rates were lower in the essential ICSI group as compared with the non-essential ICSI group (21 versus 32% respectively; P < 0.05) and 26% for IVF embryos. In conclusion, essential ICSI was associated with lower fertilization and implantation rates.

Adult↗

Outcome of IVF in DES-exposed daughters: experience in the 90s.

PURPOSE: The outcome of in vitro fertilization (IVF) in a group of infertile women with a history of in utero exposure to diethylstilbestrol (DES) was analyzed. Records from an academic IVF program were retrospectively reviewed. METHODS: Seventeen infertile women with a self-reported history of exposure to DES in utero, attending the IVF unit at Massachusetts General Hospital (MGH) for assisted reproductive technology (ART), underwent 27 IVF cycles. Analysis of the outcome of IVF including implantation and ongoing pregnancy rates was performed. The data were compared with results from a group of 20 infertile patients with idiopathic infertility undergoing 27 IVF cycles at MGH during the same period. The patients in the two groups were matched for age, basal day 3 levels of follicle stimulating hormone and serum estradiol, and the number and quality of embryos transferred. RESULTS: The response to controlled ovarian hyperstimulation was comparable in the two groups. Significantly lower implantation and ongoing pregnancy rates following IVF and embryo transfer were seen in the utero DES-exposed group compared to the control patients. CONCLUSIONS: Infertile patients with a history of in utero exposure to DES exhibit a significantly impaired implantation rate following IVF, and the outcome of ART remains poor.

Adult↗

The physical and psychomotor development of children conceived by IVF and exposed to high-frequency vaginal ultrasonography (6.5 MHz) in the first trimester of pregnancy.

We examined the physical and psychomotor development of 33 infants conceived by in vitro fertilization (IVF) who were exposed to high-frequency transvaginal ultrasonography (HFTVS) (6.5 MHz) in the first trimester of pregnancy. The study group was composed of 21 singletons and six sets of twins. Thirty-three non-IVF controls were matched for birth weight, gestational age, sex, birth order, order in multiple delivery, mode of delivery, age at examination and parental age and education. Forty-five IVF infants who were not exposed to HFTVS and their matched controls also served as comparison groups. The Bayley scales were used to assess the psychosocial development of the infants studied. Increases in preterm delivery, low birth weight and Cesarean section rates were within the acceptable range for IVF babies. Mean birth weight, gestational age and birth weight percentiles of exposed IVF infants were lower than the expected mean for a normal population, but did not differ from that of non-exposed IVF infants. Mean percentiles of weight and length at examination were also low but not different from those of non-exposed IVF and matched control groups. However, percentiles of head circumference were normal at birth and at examination both in study and control groups. Overall, Bayley scores of exposed IVF infants were within the normal range and did not differ significantly from those of their matched controls and non-exposed peers. These scores were significantly correlated to birth weight, percentiles of birth weight and head circumference at birth and at examination, and to the mother's education. Twins had lower physical and mental indices than singletons, but did not differ from their controls.

Journal Article↗

Equity in the use of IVF in Finland in the late 1990s.

AIMS: The purpose of this study was to describe equity in the use of in vitro fertilization (IVF; including micro-injections and frozen-embryo transfers), and compare its use with that of other assisted reproduction technologies (other ARTs; including ovulation inductions with or without inseminations). METHODS: The women who received IVF (n=9, 175) and other ARTs (n=10,254) between 1996 and 1998 were identified from the reimbursement records of the Social Insurance Institution (SII) covering all Finns. Population controls, matched by age and municipality, were selected for IVF women (n=9,175). Information concerning background characteristics came from the Central Population Register and the SII's reimbursement files. The sector (public vs. private) was defined using prescribing physicians' codes. IVF use was studied by the proportions of women treated and the frequency of treatment. RESULTS: The age-standardized IVF incidence per thousand 20-to-49-year-old women was 8.8 in urban and 7.3 in rural areas, but the use of other ARTs did not vary correspondingly (9.2, 9.3). The regional incidence of IVF and other ARTs varied considerably. In the private sector, women in the highest socioeconomic position were over-represented (29% private, 18% public, 16% controls). During the mean 1.5 years of the study period, the IVF women had somewhat more treatment cycles in the private than in the public sector (mean 3.3, 2.7), and those in the highest socioeconomic position had more cycles than others (3.5, 3.2); the frequency was not age-dependent. In the public sector the number of cycles did not differ by socioeconomic group (mean 2.7-2.8 per woman), and women aged 25 to 39 had more cycles than others. CONCLUSION: There were socioeconomic differences in use of IVF services, but they were small because of the equitable use of public services.

Adult↗

The outcome of twin pregnancies after IVF.

It has been suggested that the high rates of prematurity, low birth weight, perinatal morbidity and mortality in in-vitro fertilization (IVF) infants are due to the increased frequency of multiple gestations in this population. The aim of our study was to test this hypothesis by comparing the outcome of IVF twins with that of twins born after spontaneously conceived pregnancies. The perinatal outcome of 40 IVF twins was compared with that of 80 control twins, matched for maternal age, parity and ethnic origin. IVF twins had a higher rate of prematurity (P = 0.03), their mean birth weight was significantly lower (P < 0.01) and the frequency of very low birth weight infants was much higher (P < 0.003). There was no neonatal mortality in the control group, whereas four IVF twins died (P < 0.01). Neonatal morbidity was significantly greater in IVF twins (P < 0.05). Oxygen therapy and mechanical ventilation were administered more frequently to IVF twins (P < 0.007 and P < 0.05). We conclude that twins conceived by IVF are at a significantly higher risk for prematurity and associated neonatal morbidity and mortality than spontaneously conceived twins.

Adult↗

Comparison between day-2 embryos obtained either from ICSI or resulting from short insemination IVF: influence of maternal age.

Short incubation time prevents deleterious effects of cumulus cell degeneration and excess spermatozoa in IVF embryos. We performed a short incubation (3 h) protocol in 328 IVF cycles, in order to compare the developmental potential of regular IVF embryos with those originating from 316 cycles entered our intracytoplasmic sperm injection (ICSI) programme over the same period. Embryo transfers were performed in all patients on day 2. The mean number of embryos transferred was 1.92 for the ICSI group and 1.73 for the IVF group (P < 0.007). This was related only to the wishes of patients. However, the policy of the centre is to transfer a low number of embryos in young patients in order to avoid multiple pregnancies. All spare embryos were permitted to grow to the blastocyst stage for freezing. Shortening incubation time did not decrease fertilization rates. In our overall population, no difference was observed in the implantation rates per embryo for IVF (19%) or for ICSI (20%). An age-related decrease in embryo production was observed for both groups of patients (P < 0.01 for ICSI and P < 0.001 for IVF). The age-related decrease in embryo implantation was only significant for the IVF group (P < 0.03 for patients <30 and >35 years of age). A significant overall decrease in blastocyst formation was observed for spare embryos after ICSI versus IVF (34.2 versus 43.8%; P < 0. 05). The significance of this observation is discussed.

Adult↗

Growth, psychomotor development and morbidity up to 3 years of age in children born after IVF.

BACKGROUND: To examine the long-term child outcome after IVF until the age of 3 years in Northern Finland, we conducted a population-based cohort study. METHODS: First, a cohort of 299 IVF children born in 1990-1995 was compared with a cohort of 558 controls representing the general population in terms of a multiple birth rate of 1.2%, randomly chosen from the Finnish Medical Birth Register (FMBR) and matched for sex, year of birth, area of residence, parity, maternal age and social class (full sample analyses). Second, IVF singletons (n = 150) were compared with singleton controls (n = 280). Third, a plurality matched control cohort (n = 100) for IVF twins (n = 100) was randomly chosen, matched as above, from the FMBR and analysed separately. Infant mortality rate was compared with the national rate from the FMBR. RESULTS: Infant mortality in the IVF group was >2-fold higher compared to the national rate in the general population. The risk (OR, 95% CI) of low weight and height, below the lowest quartile, at 1 year of age (1.6, 1.1-2.2; 1.6, 1.1-2.4) and 2 years of age (1.5, 1.1-2.4; 1.7, 1.2-2.5) was significantly higher in the IVF group when compared with the general population control group. No statistically significant differences were found in the psychomotor development between the cohorts. Cumulative incidence of different diseases up to 3 years of age was significantly higher among IVF children in the full sample and singleton analyses (OR, 95% CI: 2.3, 1.7-3.2; 2.1, 1.3-3.3 respectively) especially regarding respiratory diseases (3.5, 1.9-6.5; 3.1, 1.0-9.4) and diarrhoea (3.7, 2.2-6.2; 5.7, 2.6-12.7), but not in twin comparisons. CONCLUSIONS: The growth of IVF children was behind that of control children during the first 3 years of life, but their psychomotor development was similar. Their postnatal health was worse, probably reflecting the problems in the neonatal period.

Body Height↗

What is the most relevant standard of success in assisted reproduction? The next step to improving outcomes of IVF: consider the whole treatment.

Changing the way in which successful IVF treatment is defined offers a tool to improve efficacy while reducing costs and complications of treatment. Crucial to this paradigm shift is the move away from considering outcomes in terms of the single IVF cycle, and towards the started IVF treatment as a whole. We propose the most informative end-point of success in IVF to be the term singleton birth rate per started IVF treatment (or per given time period) in the overall context of patient discomfort, complications and costs. These end-points are important not only for patients, but also for clinicians, health economists and policy makers. Such an approach would encourage the development of patient-friendly and cheaper stimulation protocols with less stress, discomfort and side effects. The combination of mild ovarian stimulation with single embryo transfer may provide the same overall pregnancy rate per total IVF treatment, achieved in the same amount of time for similar direct costs, but with reduced patient stress and discomfort, and the near complete elimination of multiple pregnancies. This would offer major health and indirect cost benefits. If IVF success rates were to be expressed in terms of delivery of a term single baby per IVF treatment (or in a given treatment period), the introduction of single embryo transfer on a large scale would be facilitated.

Embryo Transfer↗