Attitudes of anonymous and identity-release oocyte donors towards future contact with donor offspring.

STUDY QUESTION: What are the attitudes and expectations of past oocyte donors concerning contact with their donor offspring and contact between donor offspring and their own children? SUMMARY ANSWER: The large majority (95%) of open-identity oocyte donors, as well as voluntarily registered donors (registered before the Finnish 2007 ART law), expressed positive or neutral feelings towards contact with their donor offspring and mainly positive expectations towards contact between donor offspring and their own children. WHAT IS KNOWN ALREADY: Although there is a growing support for openness and identity-release programmes in gamete donation, there is not much knowledge on how donors feel about potential contact with their offspring. Most previous studies have investigated donor expectations with a relatively short follow-up time, using small samples or participants in voluntary donor linkage services. STUDY DESIGN, SIZE, DURATION: A retrospective cross-sectional survey of all women who had donated oocytes between 1990 and 2012 at three fertility clinics in Finland was carried out in 2013. A self-administered questionnaire was sent out to a total of 569 former oocyte donors. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 428 former oocyte donors answered a questionnaire assessing experiences and attitudes related to donation (response rate 75.2%). In this study, 358 donors who were unknown to the recipient were included. The mean follow-up time after the donation was 11.2 years. Before 2008, donors were non-identifiable but could voluntarily consent to release their identifying information to their donor offspring. After 2008, persons born as a result of gamete donation can, from the age of 18, receive information identifying the donor. Altogether 290 respondents had participated in a donation programme in 1990-2007 (before the Finnish ART-law), and 68 participated after the enactment of the ART-law, enabling us to compare attitudes by type of legislation during donation. MAIN RESULTS AND THE ROLE OF CHANCE: Most voluntarily registered and open-identity donors welcomed or were neutral to potential contact with their donor offspring but were slightly more cautious towards contact between their own children and a donor-conceived child. Open-end comments revealed some ambiguity and uncertainty as to what to expect from such contact and feelings varied from neutral curiosity and interest to desire to meet the donor-conceived child. LIMITATIONS, REASON FOR CAUTION: It is not possible to assess whether the opinions of the study participants is representative of all donors in 1990-2012, as 25% of all contacted former donors did not respond to the survey. WIDER IMPLICATIONS OF THE FINDINGS: This study is one of only a few studies among oocyte donors to evaluate long-term psychosocial consequences of the donation and expectations towards contact with donor offspring, using a large sample. Results from this study show that persisting concerns about adverse outcomes of identity release policies are largely unwarranted, but there is a need to develop counselling practices and material for identity-release donors about how to prepare for and adjust to potential contact with donor offspring. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Medical Society Life and Health, and from the Otto A. Malm Foundation. The authors have no competing interests to report. TRIAL REGISTRATION NUMBER: N/A.

Obstetric and neonatal complications in pregnancies conceived after oocyte donation: a systematic review and meta-analysis.

BACKGROUND: Approximately 50 000 oocyte donation (OD) treatment cycles are now performed annually in Europe and the US. OBJECTIVES: To ascertain whether the risk of adverse obstetric and perinatal/neonatal outcomes is higher in pregnancies conceived by OD than in pregnancies conceived by conventional in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) or spontaneously. SEARCH STRATEGY: A systematic search was performed in the PubMed, Cochrane and Embase databases from 1982-2016. Primary outcomes were hypertensive disorders of pregnancy, pre-eclampsia (PE), gestational diabetes mellitus, postpartum haemorrhage, caesarean section, preterm birth, low birthweight and small for gestational age. SELECTION CRITERIA: Inclusion criteria were original studies including at least five OD pregnancies with a control group of pregnancies conceived by conventional IVF/ICSI or spontaneous conception, and case series with >500 cases reporting one or more of the selected complications. Studies not adjusting for plurality were excluded. DATA COLLECTION AND ANALYSIS: Thirty-five studies met the inclusion criteria. A random-effects model was used for the meta-analyses. MAIN RESULTS: For OD pregnancies versus conventional IVF/ICSI pregnancies the risk of PE was adjusted odds ratio (AOR) 2.11 (95% CI, 1.42-3.15) in singleton and AOR 3.31 (95% CI, 1.61-6.80) in multiple pregnancies. The risks of preterm birth and low birthweight in singletons were AOR 1.75 (95% CI, 1.39-2.20) and 1.53 (95% CI, 1.16-2.01), respectively. CONCLUSIONS: OD conceptions are associated with adverse obstetric and neonatal outcomes. To avoid the additional increase in risk from multiplicity, single-embryo transfer should be the choice of option in OD cycles. TWEETABLE ABSTRACT: Oocyte donation pregnancies have increased risk of a range of obstetric and neonatal complications.

Attitudes and disclosure decisions of Finnish parents with children conceived using donor sperm.

STUDY QUESTION: What are disclosure intentions and experiences of heterosexual parents with children born after assisted donor insemination (DI) or IVF with donor sperm (dIVF)? SUMMARY ANSWER: Only 16.5% of Finnish DI/dIVF heterosexual parents had told their child of his/her origin; 18% of all children above 3 years of age had received the information. Parents with older children were more unwilling to tell or were more uncertain regarding what to do than parents with younger children. WHAT IS KNOWN ALREADY: In general, 10-35% of parents of DI offspring are willing to inform their child about their conception. Men who need donor sperm to become a father are more secretive than women who need donated oocytes and are less willing to participate in counselling about parenthood. In the past, couples conceiving through gamete donation were adviced to maintain secrecy or sufficient advice on information sharing was not available. Evidence suggests that parental attitudes are moving towards greater openness. In 2007, Finland enacted a law on assisted fertility treatments (1237/2006) stating that gamete donors have to register their identifying information in a registry so that at the age of 18 years, offspring can obtain information about their donor. STUDY DESIGN, SIZE AND DURATION: This retrospective questionnaire study included 139 mothers and 127 fathers with altogether 240 children born after DI or dIVF during 1992-2007. PARTICIPANTS, SETTING AND METHODS: Questionnaires were sent to heterosexual couples who had undergone DI/dIVF treatment at the Väestöliitto Fertility Clinic in Helsinki resulting in live birth (n = 277, 252 mothers and 239 fathers). The parents were asked to report their disclosure intentions towards the child and towards other people about the decision to use donated sperm, their concerns about donor characteristics, their evaluation of the counselling that they received and their views about the current Finnish assisted reproduction law. MAIN RESULTS AND THE ROLE OF CHANCE: The response rate was 55% (139/252) among the mothers and 53% (127/239) among the fathers. Answers provided information on 58% (240/415) of the children born, 91% of whom were at least 3 years old at the time. Of all parents, 16.5% reported that they had already told their child of his/her conception. Of all 240 children, 16.3% had already received information about their conception. The children had been between 3 and 14 years of age (mean 6.8 years) when they were told. Parents of older children were significantly more unwilling to tell their child than parents of younger children (P < 0.005). No difference in disclosure between DI and dIVF emerged. Less than half of the parents (42%) had been satisfied with the psychological support offered to them, with parents of older children having been most dissatisfied. LIMITATIONS, REASONS FOR CAUTION: Although the response rate was relatively high, more than 40% of the parents chose not to participate. As has been shown before, it is likely that those who do not take part are less inclined to disclose and this should be taken into consideration when conclusions are drawn. WIDER IMPLICATIONS OF THE FINDINGS: Our results on disclosure rates are in agreement with previous studies. General attitudes have moved towards greater openness about the use of donated gametes. Furthermore, the availability of psychological counselling before treatment has increased the understanding of the importance of disclosure. People who have become parents after DI or dIVF should also be offered counselling after the child has been born. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from the Wilhelm and Else Stockmann Foundation and the Medical Society Life and Health. There are no competing interests to disclose. TRIAL REGISTRATION NUMBER: None.

Elective single-embryo transfer in women aged 40-44 years.

STUDY QUESTION: Is an elective single-embryo transfer (eSET) policy feasible for women aged 40 or older? SUMMARY ANSWER: For older women (aged 40-44 years) with a good prognosis, an eSET policy can be applied with acceptable cumulative clinical pregnancy rates and live birth rates. WHAT IS KNOWN ALREADY: Various studies have shown the effectiveness of eSET in women aged <35 years with high cumulative pregnancy rates and low rates of multiple births. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 628 women treated between 2000 and 2009. PARTICIPANTS, SETTING, METHODS: Women aged 40-44 years underwent a fresh cycle of IVF or ICSI treatment with eSET (n = 264) or double-embryo transfer (DET) (n = 364). In the subsequent frozen-thawed embryo transfer cycles, SET/DET was performed in both groups according to the number of embryos available and the opinion of the couple. The study was performed at the Family Federation of Finland Helsinki Fertility Clinic. MAIN RESULTS AND THE ROLE OF CHANCE: In the fresh cycles, the clinical pregnancy rates were 23.5 and 19.5% in the eSET and DET groups, respectively, and live birth rates were 13.6 and 11.0%, respectively. In the fresh cycles with eSET, there were no twin pregnancies, but in the DET group, there were three sets of twins (7.5%). The cumulative clinical pregnancy rates per oocyte retrieval were 37.1 and 24.2% in the eSET and DET groups, respectively (P < 0.001), and the cumulative live birth rates were 22.7 and 13.2%, respectively (P = 0.002). Cumulative twin rates were 6.7% (n = 4) in the eSET group and 8.3% (n = 4) in the DET group (P = 0.726). All of the twin pregnancies in the eSET group resulted from frozen and thawed DET embryo transfer cycles. LIMITATIONS: The characteristics of the two patients groups are not comparable because the suitability of eSET was individually assessed by a clinician based on both clinical prognostic factors and the outcome of IVF or ICSI, i.e. the number and quality of embryos. WIDER IMPLICATIONS OF THE FINDINGS: This study may be generalized to IVF units having experience in eSET and cryopreservation.

Does long in vitro culture promote large for gestational age babies?

STUDY QUESTION: Does the length of time during which embryos are cultured in vitro affect the birthweight of the infants? SUMMARY ANSWER: The duration of the embryo culture period is a significant factor in determining the birthweight of the infants. WHAT IS ALREADY KNOWN: IVF children show adverse perinatal outcome when compared with the general population and increased incidence of preterm birth and low birthweight is commonly observed. STUDY DESIGN, SIZE, DURATION: A retrospective cross-sectional cohort study including 1079 infants born after treatment at the Family Federation of Finland Fertility Clinic in Helsinki, between 2000 and 2010. PARTICIPANTS, SETTING, METHODS: All singleton IVF children were included. The gestation- and gender-adjusted birthweights of the babies were analyzed according to mother's age, BMI, and parity, type of treatment (IVF or ICSI), main cause of infertility and embryo culture period. Two outcomes were investigated: the birthweight and the proportion of small and large for gestational age (SGA and LGA) infants. Multiple linear regression analysis was performed to show the significance of each individual factor on determining the birthweight of the babies born. MAIN RESULTS AND THE ROLE OF CHANCE: In the study group as a whole, the distribution of the SGA and LGA babies showed no deviation from the growth charts of the general population. However, when the birthweight of the children was analyzed according to the length of embryo culture from Day 2 to Days 5-6, an increase in the proportion of LGA babies was found (D2 9.4%, D3 11.5%, D5-6 18.8%; D2 n = 871, D3 n = 139, D5-6 n = 69). Multiple linear regression analysis showed that BMI (P < 0.001) and parity (P < 0.001) of the mother, as well as the embryo culture period (P = 0.007) had a significant effect on the birthweight. The value of the adjusted R(2) was 0.437. LIMITATIONS, REASONS FOR CAUTION: Small number of D5-6 infants and a lack of pregnancy-associated factors contributing to birthweight. WIDER IMPLICATIONS OF THE FINDING: This study warrants larger studies to analyze the birthweight of the IVF children, particularly after blastocyst culture. STUDY FUNDING/COMPETING INTEREST: The study was funded by the Family Federation of Finland, Fertility Clinic Helsinki. No competing interests.

Obstetric and perinatal risks after the use of donor sperm: A systematic review and meta-analysis.

Donor sperm is widely used in infertility treatments. The purpose of the study was to investigate, whether use of donor sperm in intrauterine insemination (IUI) or in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments affect maternal and perinatal risks compared with spontaneously conceived pregnancies or use of partner sperm in IUI, IVF or ICSI. We provide a systematic review and meta-analyses on the most clinically relevant obstetric and perinatal outcomes after use of donor sperm compared with partner sperm: hypertensive disorders of pregnancy, preeclampsia, low birth weight, and preterm birth. Our meta-analyses showed an increased risk for preeclampsia (pooled adjusted odds ratio (aOR) 1.77, 95% CI 1.26-2.48) and hypertensive disorders of pregnancy (pooled aOR 1.55, 95%, CI 1.20-2.00) in pregnancies resulting from IUI with donor sperm compared with IUI with partner sperm. No increased risk was seen for low birth weight or preterm birth after the use of donor sperm in IUI compared with the use of partner sperm in IUI. Subgroup analysis for singletons only did not change these results. The meta-analysis on low birth weight showed a lower risk after in IVF with donor sperm compared with IVF with partner sperm (pooled aOR 0.89, 95% CI 0.83-0.94). For hypertensive disorders of pregnancy, preeclampsia and preterm birth, no difference was found between IVF with donor sperm vs. partner sperm. Patients need to be informed about the moderately increased risk of hypertensive disorders of pregnancy and preeclampsia in pregnancies after IUI with donor sperm.

Increasing openness in oocyte donation families regarding disclosure over 15 years.

BACKGROUND: Worldwide there is an increasing number of families created by oocyte donation (OD). The aim of this study was to gather information about parents' plans of disclosure to their child and to other people, as well as parents' attitudes and level of satisfaction up to 15 years after their OD treatment. METHODS: A questionnaire with separate material for each partner was sent to all parents (167 mothers, 163 fathers) who had had a child after treatment with donated oocytes at Väestöliitto Fertility Clinics in Helsinki during 1992-2006. These parents had a total of 231 children aged 1-14 years. Parents were asked if they had told or intended to tell their child about his/her origin and how and when they had done so and about the reasons to disclose or not. Other questions were about openness towards other people, concerns about donor characteristics, counselling and feelings towards the child. RESULTS: Of the mothers, 61.1%, and of the fathers, 60.0%, had told or intended to tell the child of his/her conception. Of children over 3 years of age, 26% had already been informed. There was a statistically significant difference between parental telling in different age groups of children (P = 0.011, χ(2)). In the youngest age group (1-3 years), 83.3% of parents were inclined to disclosure compared with 44.4% in the oldest age group (13-14 years). A high proportion of mothers (86.7%) and fathers (71.0%) had told other people about the nature of their child's conception. The majority of parents did not have much concern about the characteristics of the donor. A higher proportion of the mothers (24%) compared with fathers (11%) thought that the psychological support had been insufficient. They thought that discussions with health professionals should be arranged routinely after delivery or when it was time to inform the child. CONCLUSIONS: Parents with young OD children are clearly more inclined to disclosure compared with parents with older children.

Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data.

BACKGROUND: An estimated 3.5 million children have been born to date using assisted reproduction technologies. We reviewed the data in order to evaluate current knowledge of medical outcome for IVF/ICSI children born after cryopreservation, slow freezing and vitrification of early cleavage stage embryos, blastocysts and oocytes. METHODS: A systematic review was performed. We searched the PubMed, Cochrane and Embase databases from 1984 to September 2008. Inclusion criteria for slow freezing of early cleavage stage embryos were controlled studies reporting perinatal or child outcomes. For slow freezing and vitrification of blastocysts and oocytes, and vitrification of early cleavage stage embryos, case reports on perinatal or child outcomes were also included. Three reviewers independently read and evaluated all selected studies. RESULTS: For early cleavage embryos, data from controlled studies indicated a better or at least as good obstetric outcome, measured as preterm birth and low birthweight for children born after cryopreservation, as compared with children born after fresh cycles. Most studies found comparable malformation rates between frozen and fresh IVF/ICSI. For slow freezing of blastocysts and for vitrification of early cleavage stage embryos, blastocysts and oocytes, limited neonatal data was reported. We found no long-term child follow-up data for any cryopreservation technique. CONCLUSION: Data concerning infant outcome after slow freezing of embryos was reassuring. Properly controlled follow-up studies of neonatal outcome are needed after slow freezing of blastocysts and after vitrification of early cleavage stage embryos, blastocysts and oocytes. In addition, child long-term follow-up studies for all cryopreservation techniques are essential.

Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis.

BACKGROUND: Assisted reproduction technology (ART) is used worldwide, at increasing rates, and data show that some adverse outcomes occur more frequently than following spontaneous conception (SC). Possible explanatory factors for the well-known adverse perinatal outcome in ART singletons were evaluated. METHODS: PubMed and Cochrane databases from 1982 to 2012 were searched. Studies using donor or frozen oocytes were excluded, as well as those with no control group or including <100 children. The main outcome measure was preterm birth (PTB defined as delivery <37 weeks of gestation), and a random effects model was used for meta-analyses of PTB. Other outcomes were very PTB, low-birthweight (LBW), very LBW, small for gestational age and perinatal mortality. RESULTS: The search returned 1255 articles and 65 of these met the inclusion criteria. The following were identified as predictors for PTB in singletons: SC in couples with time to pregnancy (TTP) > 1 year versus SC singletons in couples with TTP ≤ 1 year [adjusted odds ratio (AOR) 1.35, 95% confidence interval (CI) 1.22, 1.50]; IVF/ICSI versus SC singletons from subfertile couples (TTP > 1 year; AOR 1.55, 95% CI 1.30, 1.85); conception after ovulation induction and/or intrauterine insemination versus SC singletons where TTP ≤ 1 year (AOR 1.45, 95% CI 1.21, 1.74); IVF/ICSI singletons versus their non-ART singleton siblings (AOR 1.27, 95% CI 1.08, 1.49). The risk of PTB in singletons with a 'vanishing co-twin' versus from a single gestation was AOR of 1.73 (95% CI 1.54, 1.94) in the narrative data. ICSI versus IVF (AOR 0.80, 95% CI 0.69-0.93), and frozen embryo transfer versus fresh embryo transfer (AOR 0.85, 95% CI 0.76, 0.94) were associated with a lower risk of PTB. CONCLUSIONS: Subfertility is a major risk factor for adverse perinatal outcome in ART singletons, however, even in the same mother an ART singleton has a poorer outcome than the non-ART sibling; hence, factors related to the hormone stimulation and/or IVF methods per se also may play a part. Further research is required into mechanisms of epigenetic modification in human embryos and the effects of cryopreservation on this, whether milder ovarian stimulation regimens can improve embryo quality and endometrial conditions, and whether longer culture times for embryos has a negative influence on the perinatal outcome.

Pregnancy and child outcome after oocyte donation.

During the last decade oocyte donation has been highly successful for treating women previously thought to be hopelessly infertile. The pregnancy rate after oocyte donation is among the highest reported for any fertility-enhancing procedure. Most investigators have noted an increased rate of obstetric complications in these pregnancies. In particular, pregnancy-induced hypertension appears to occur more often than expected, and the Caesarean section rate is high. However, the majority of oocyte recipients experience a favourable pregnancy and perinatal outcome. When perinatal complications occur they are usually related to multiple gestation. The high frequency of multiple pregnancy after oocyte donation, as well as in all other fields of assisted reproduction, deserves attention, and efforts to avoid multi-fetal gestation must be made. There are only a few studies on post-natal growth and development of young children born after oocyte donation. The health of these children appears to be within normal ranges. The psychological consequences of the treatment on the child require further investigation. Thus far, studies have shown normal socio-emotional development in the child and a warm relationship between the parents and the child in oocyte donation families.

Follow-up study of Finnish volunteer oocyte donors concerning their attitudes to oocyte donation.

A questionnaire was sent to the first 30 Finnish volunteer oocyte donors at 12-18 months after donation to determine their experiences concerning treatment and attitudes to donation. All donations were carried out anonymously and without payment. The donors were recruited by advertising in newspapers. Most donors were very satisfied with the experience. The side-effects of the treatment had been slight and tolerable. In all, 85% of the respondents reported no gynaecological problems afterwards. The problems reported by the other 15% were minor and unrelated to the donation. A total of 67% of the respondents would have liked to have known if pregnancy had been achieved in the recipient, and 89% reported that they had thought about the possibility of a child from their donation. Some 42% of the respondents preferred to receive no information concerning either the child or the recipient couple. Of the respondents, 59% thought the offspring should be told about its origin and 33% thought the child should be given identifying information about the donor. About half of the others would agree to the release of non-identifying information. In all, 96% of the respondents reported that their own feelings were sufficiently taken into consideration during the treatment and 78% would donate again. No-one regretted their donation.

An oocyte donation program with goserelin down-regulation of voluntary donors.

BACKGROUND: In ovum donation programs oocytes can be requested from infertile women going through an in vitro fertilization cycle. Currently, when embryos can be cryopreserved, these donors have virtually disappeared. Instead, most donors have been healthy fertile volunteers willing to go through an IVF attempt solely for the purpose of donating all oocytes. METHODS: Sixty-four patients had 93 started cycles of oocyte donation from 59 donors. Twenty recipients had primary ovarian failure, 24 had secondary ovarian failure, 15 had had repeated failures in earlier IVF attempts and five were carriers of genetic diseases. The donors were 51 healthy volunteers recruited through the press. Eight patients from an IVF program donated excess oocytes. Donors were not paid and their mean age was 30 years. To minimize discomfort of the treatment, a long-acting GnRH-agonist, goserelin, was used for down-regulation. RESULTS: The pregnancy rate per transfer with fresh embryos was 28.4% (23/81) and with frozen-thawed embryos, 17% (3/18). Twenty-one healthy infants have been born including one set of triplets and three sets of twins. Nine pregnancies ended in abortion and one in intrauterine fetal death. The most common complications of pregnancy were pre-eclampsia and pregnancy-induced hypertension (41.2%, 7/17). Ten of 17 patients delivered by cesarean section (58.8%). CONCLUSION: It was possible, through the press, to obtain highly motivated oocyte donors, who go through IVF treatment solely for altruistic reasons. Oocyte recipients appear to have many complications in their pregnancies. Until more data are available, these patients need a high standard of obstetric care.

Levonorgestrel-releasing intrauterine device can be used in oocyte donors during ovarian stimulation.

Seven oocyte donors with a levonorgestrel-releasing intrauterine device (LNG-IUD) in situ (group A) underwent ovarian stimulation with human menopausal gonadotrophin (HMG) after goserelin down-regulation, in eight treatment cycles. The donors in a control group (group B, n = 16) were comparable in age, body mass index and parity characteristics. There were no statistically significant differences in response to ovarian hyperstimulation between the two groups. The number of oocytes recovered was 12.4 +/- 5.1 (SD) following stimulation with 27.9 +/- 9.3 ampoules of HMG over 11.2 +/- 1.3 days in group A. Following stimulation with 26.2 +/- 6.3 ampoules of HMG over 11.0 +/- 1.0 days, the number of oocytes collected was 13.9 +/- 10.4 in group B. The fertilization rate (2PN/cell) of cells in group A was 63% (62/99) and in group B, 53% (117/220, not significant). The cleavage rate of cells in group A (60%, 59/99) was significantly higher than in group B (47%, 104/220) (P <0.05). On average, two embryos were transferred per cycle. In group A, the pregnancy rate per transfer was 40% (4/10) and in group B, 29% (6/21; not significant). In conclusion, LNG-IUD can be used as a contraceptive method during ovarian stimulation of volunteer oocyte donors.

A randomized comparative study of highly purified follicle stimulating hormone and human menopausal gonadotrophin for ovarian hyperstimulation in an oocyte donation programme.

A randomized comparative study of highly purified human follicle-stimulating hormone (FSH-HP), administered s.c., and human menopausal gonadotrophin (HMG), administered i.m., was carried out in 41 volunteer oocyte donors. The response to ovarian hyperstimulation was similar in both groups. One cycle in both groups was cancelled. The number of oocytes recovered was 16.0 +/- 7.9 (mean +/- SD) following stimulation with 32.8 +/- 10.3 ampoules of FSH-HP (n = 19) over 12.3 +/- 1.7 days. Following stimulation with 29.8 +/- 10.6 ampoules of HMG over 11.5 +/- 1.6 days, the number of oocytes collected was 18.4 +/- 12.7 (n = 20). The oocyte recipients were allocated 9.2 +/- 3.6 oocytes in the FSH-HP group (n = 33) and 9.6 +/- 4.6 oocytes in the HMG group (n = 37). The fertilization rate (2PN/cell) was significantly higher in the HMG group (48%, 170/355) than in the FSH-HP group (36%, 109/304) (P < 0.01). The number of embryos transferred per recipient was 2.0 +/- 0.4 in the FSH-HP and 2.0 +/- 0.3 in the HMG group. The pregnancy rate per embryo transfer was 25% in the FSH-HP (5/20) and 26% (8/31) in the HMG group. Fertile donors with body mass index > or = 25 made up a poor responder group to s.c. FSH-HP, possibly indicating reduced absorption of the drug.

Turner's syndrome and pregnancies after oocyte donation.

A total of 20 clinical pregnancies was achieved among 18 women with Turner's syndrome who were treated in an oocyte donation programme. The oocytes were donated by voluntary unpaid donors. A mean of 1.8 embryos per transfer was given to each recipient by way of 28 fresh and 25 frozen embryo transfers. With fresh and frozen embryos, 13 and seven pregnancies respectively were achieved. The clinical pregnancy rate per fresh embryo transfer was 46%, and the implantation rate 30%, being similar to the corresponding rates among our oocyte recipients with primary ovarian failure in general. The corresponding rates with frozen embryos were 28 and 19%. Of these pregnancies, 40% ended in miscarriage. This high rate may be explained by uterine factors. Six women were hypertensive during pregnancy, a rate comparable with that in other oocyte donation pregnancies. All these women delivered by Caesarean section. Pregnancy and implantation rates after oocyte donation were high in women with Turner's syndrome, but the risk of cardiovascular and other complications is high. Careful assessment before and during follow-up of pregnancy are important. Transfer of only one embryo at a time to avoid the additional complications caused by twin pregnancy is recommended.

Health and development of children born after oocyte donation compared with that of those born after in-vitro fertilization, and parents' attitudes regarding secrecy.

The health, growth and development of a cohort of children (n = 59) aged 6 months to 4 years and born after oocyte donation (OD) was compared with that from a group of children born after in-vitro fertilization (IVF) (n = 126). The study was performed by questionnaire, and the response rate was 100% in the OD group and 95% in the IVF group. All OD children were healthy. Three IVF children had a neurological disorder. Surgical intervention had been carried out in 8% of the OD and 13% of the IVF children. Height and weight development were normal, and eating and sleeping disorders were uncommon in both groups of children. The IVF mothers more often expressed concern about the child's behaviour than did the OD mothers. Thirty-eight percent of the OD parents and 60% of the IVF parents intended to tell the child about the nature of its conception (P < 0.01). Although oocyte recipients appear to have more complications during their pregnancies than conventional IVF patients, the general health status of OD children aged <5 years is at least as good as that of IVF children. Growth and development in both groups of children is similar to that of the general population.

Obstetric and perinatal outcome after oocyte donation: comparison with in-vitro fertilization pregnancies.

The obstetric and perinatal outcome in 51 oocyte donation pregnancies (61 infants) was compared with that of a control group of standard in-vitro fertilization (IVF) patients (97 pregnancies, 126 infants). The oocyte recipients (mean +/- SD age 33.5+/-4.7 years) included 39 women with ovarian failure and 12 women with functioning ovaries. In oocyte recipients, first trimester bleeding (53%) occurred significantly more often than in IVF mothers (31%, P < 0.01). Pregnancy-induced hypertension was observed in 31% of oocyte recipients compared with 14% in IVF mothers (P < 0.05). There was no difference in the duration of pregnancies or in the preterm delivery rate between the two groups. When restricting analysis to singleton pregnancies, 63% of oocyte recipients were hospitalized in the antenatal period compared with 29% in the IVF group (P < 0.001). The Caesarean section rate was 57% in the oocyte donation group and 37% in the IVF group (P < 0.05). Birthweight in singleton pregnancies was similar in both groups. The perinatal mortality rate was 3.3% in the oocyte donation group and 0% in the IVF group. In conclusion, oocyte donation pregnancies are associated with an increased risk compared with IVF pregnancies, but the complications are usually manageable and most oocyte recipients experience a good pregnancy outcome.

Embryo donation: outcome and attitudes among embryo donors and recipients.

The outcome of an embryo donation programme was evaluated and attitudes among donors and recipients studied by means of a questionnaire survey. A total of 27 couples went through 54 treatment cycles with frozen-thawed embryos donated by other infertile couples. The indications for treatment were premature or incipient ovarian failure in combination with severe male factor infertility. The mean age of the recipient women was 36 years, and that of the recipient men was 35 years. The mean duration of infertility was 8 years (range 2-19 years). Forty-six couples donated 209 excess frozen embryos to the programme. The clinical pregnancy rate in the recipients was 27.8% (15/54) per embryo transfer. An average of 1.9 embryos were transferred on each occasion. The response rate to the questionnaire was high (80-91%). Significantly more recipients (69%) than donors (47%) considered that the child should be informed about the manner of conception (P < 0.05). Some 29% of recipients and 42% of donors thought that the child should receive identifying information concerning the donor couple. The interest of the offspring, not only as regards knowing his/her genetic origin but also knowing full-blood genetic siblings, should be kept in mind in embryo donation programmes.

Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production.

Early pregnancies in women with a history of recurrent spontaneous abortion (RSA) are accompanied by a deficiency in vasodilatory and anti-aggregatory prostacyclin (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2). We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production and on pregnancy outcome in RSA women with and without detectable anticardiolipin antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33 (six with elevated and 27 with normal ACA concentrations) were randomized to receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed period to delivery. Treatment with LDA inhibited platelet TXA2 production similarly in RSA women with and without detectable ACA and with continuing pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group, mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0 ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/- 0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001 respectively), but did not affect the excretion of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha). Early pregnancy ultrasound examination revealed a living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with elevated and three with normal ACA concentrations) and five in the PLA group (17.9%, two with elevated and three with normal ACA concentrations; not significant) experienced a miscarriage. All infants were healthy, and the frequency of growth retardation was similar in both groups (13.0%). One woman in the LDA group (4.3%) and three women receiving PLA (13.0%) developed pre-eclampsia (not significant). Therefore, although treatment with LDA caused a desirable biochemical effect, it did not improve pregnancy outcome in RSA women with or without detectable ACA.

Comparison of two recombinant follicle-stimulating hormone preparations in in-vitro fertilization: a randomized clinical study.

A randomized comparison of two recombinant human follicle-stimulating hormone (recFSH) preparations (Gonal-F and Puregon) in ovarian stimulation for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was carried out at the Infertility Clinic of the Family Federation of Finland. A total of 348 women (aged 22-43 years) suffering from infertility due to miscellaneous causes was recruited. Of these, 344 underwent stimulation using equal starting doses (150 IU/day: Gonal-F n = 164, Puregon n = 158 or 300 IU/day: Gonal-F n = 8, Puregon n = 14) after down-regulation with intranasal buserelin from the mid-luteal phase. Similar clinical pregnancy rates were achieved with both preparations; 33.5% per cycle and 37.4% per embryo transfer (24.5% one-embryo and 75.5% two-embryo transfers, n = 147) with Gonal-F (150 IU/day) and 32.9% per cycle and 36.4% per embryo transfer (30.1% one-embryo and 69.9% two-embryo transfers, n = 145) with Puregon (150 IU/day). The ongoing cumulative pregnancy rates after frozen-thawed embryo transfer were 35.4% with Gonal-F and 37.7% with Puregon. Six cycles were cancelled because of a low response (three in each group). Similar numbers of oocytes were obtained in both groups; 13.0 with 150 IU/day and 6.1 with 300 IU/day Gonal-F, and 12.4 with 150 IU/day and 7.1 with 300 IU/day Puregon. The fertilization and cleavage rates and the incidence of moderate or severe ovarian hyperstimulation syndrome (Gonal-F, 2.0% and Puregon, 0.7%) were also similar. Gonal-F and Puregon were equally and highly effective in stimulation for IVF and ICSI.