A 10-year follow-up of reproductive outcomes in women attempting motherhood after elective oocyte cryopreservation.

STUDY QUESTION: Which reproductive treatment outcomes are observed in women who underwent elective oocyte cryopreservation (EOC) and who returned to the clinic with a desire for a child? SUMMARY ANSWER: Whether to warm oocytes or to first use fresh own oocytes for ART depends on age upon returning, but both strategies result in favorable reproductive outcomes. WHAT IS KNOWN ALREADY: Most affluent countries have observed a trend toward postponement of childbearing, and EOC is increasingly used based on the assumption that oocytes cryopreserved at a younger age may extend a woman's reproductive lifespan and mitigate her age-related fertility decline. Although most follow-up studies after EOC have focused on women who requested oocyte warming, a substantial proportion of women who do not conceive naturally will embark on fertility treatment without using their cryopreserved oocytes. Reports on reproductive outcomes in past EOC users are scarce, and the lack of reproductive treatment algorithms in this group of women hampers counseling toward the most efficient clinical strategy. STUDY DESIGN, SIZE, DURATION: This retrospective observational single-center study encompasses 843 women who had elective oocyte vitrification between 2009 and 2019 at our fertility clinic. Women who underwent fertility preservation for medical or oncological reasons were excluded. This study describes the outcomes of the diverse reproductive treatment strategies performed until May 2022 in women returning to our clinic to attempt motherhood. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using descriptive statistics, patient characteristics and data of ovarian stimulation (OS) of EOC cycles were analyzed, as well as data related to OS and laboratory data of ART in women who pursued fertility treatment with and/or without using their cryopreserved oocytes. The primary outcome was live birth rate (LBR) per patient after oocyte warming and after ART using fresh oocytes. Secondary outcomes were return rate, utilization rate of the cryopreserved oocytes, laboratory outcomes upon return, and LBR per embryo transfer. A multivariable regression model was developed to identify factors associated with the decision to thaw oocytes as the primary strategy and factors associated with ongoing pregnancy upon return to the clinic. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1353 EOC cycles (mean ± SD, 1.6 ± 0.9 per patient) were performed. At the time of EOC, the mean age was 36.5 ± 2.8 years, mean anti-Müllerian hormone (AMH) was 2.3 ± 2.0 ng/ml, and 174 (20.6%) women had a partner. On average, 13.9 ± 9.2 mature oocytes were cryopreserved. Two hundred thirty-one (27.4%) women returned to the clinic, an average of 39.9 ± 23.4 months after EOC. Upon returning, their mean age was 40.4 ± 3.1 years, mean AMH was 1.5 ± 1.5 ng/ml, and 158/231 (68.3%) patients had a partner. As a primary approach, 110/231 (47.6%) past EOC users embarked on oocyte warming, 50/231 (21.6%) had intrauterine insemination, and 71/231 (30.7%) had ART using fresh own oocytes. Cumulative LBR (CLBR) was 45.9% (106/231) notwithstanding a miscarriage rate (MR) of 30.7% (51/166) in the entire cohort. In total, 141 women performed oocyte warming at some stage in their treatment trajectory. A subset of 90/231 (39.0%) patients exclusively had oocyte warming (41.6 ± 3.0 years, with 10.0 ± 5.2 oocytes warmed per patient). 52/231 (22.5%) patients exclusively had ART using fresh own oocytes (mean age of 39.0 ± 2.8 years, with 9.9 ± 7.4 mature oocytes retrieved per patient). CLBR was 37/90 (41.1%) in the oocyte warming-only group and 25/52 (48.1%) in the OS-only group. MR/transfer was 25.0% and 29.3% in the oocyte warming-only group and the OS-only group, respectively. LIMITATIONS, REASONS FOR CAUTION: Both sample size and the retrospective design are limitations of this study. The decision to embark on a specific reproductive treatment strategy was based on patient preference, after counseling on their treatment options. This precludes direct comparison of the efficiency of reproductive treatment options in past EOC users in this study. WIDER IMPLICATIONS OF THE FINDINGS: Reporting on clinical outcomes of women who underwent EOC and returned to the clinic to embark on divergent reproductive treatment strategies is mandatory to establish guidelines for best clinical practice in this growing patient population. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

First live birth after fertility preservation using vitrification of oocytes in a woman with mosaic Turner syndrome.

PURPOSE: To report the case of a young woman diagnosed with Turner syndrome (TS) who achieved a live birth using her own oocytes that had been vitrified for fertility preservation. METHODS: A 25-year-old woman with mosaic (45,X/46,XX) TS was referred for fertility preservation (FP) counseling. Serum anti-Müllerian hormone (AMH) level was normal (6.4 µg/L). In view of the unpredictable rate of follicle loss in TS individuals, she requested FP and underwent two cycles of ovarian stimulation (OS) for oocyte cryopreservation (OoC) using a GnRH antagonist protocol and recombinant follicle stimulating hormone (rFSH), 200-250 IU daily for 8 resp. 12 days. RESULTS: In total, 29 metaphase II oocytes (MII) were vitrified after OS. After conceiving spontaneously and achieving a live birth, she returned to the clinic five years after OoC with a desire for pregnancy using in vitro fertilization (IVF) of her cryopreserved oocytes and preimplantation genetic testing (PGT-A). All 29 MII oocytes were thawed; 23 oocytes survived (79.3%) and were inseminated with partner sperm using intracytoplasmic sperm injection (ICSI). Thirteen oocytes were fertilized resulting in three good quality blastocysts which were vitrified after trophectoderm biopsy for PGT-A using array-CGH. Two blastocysts were found to be euploid. One was thawed and transferred to the uterus using a HRT priming protocol. An uneventful pregnancy occurred. The patient delivered a healthy baby girl weighing 3490 g at 40 weeks of gestation. CONCLUSIONS: We report the first live birth achieved using cryopreserved oocytes in a woman diagnosed with mosaic TS. Cryopreservation of oocytes after ovarian stimulation is a realistic option for FP in selected post menarche individuals with mosaic TS. Whether PGT-A may reduce the risk of pregnancy loss in TS has to be confirmed by further studies.

Preimplantation genetic testing with HLA matching: from counseling to birth and beyond.

Preimplantation genetic testing-human leukocyte antigen '(PGT-HLA) only' refers to the HLA typing of single or few cells biopsied from in vitro fertilized preimplantation embryos. The aim of the procedure is to establish a pregnancy, in which the fetus is HLA compatible with an affected sibling in need of a hematopoietic stem cell transplantation (HSCT). During PGT-M-HLA, the identification of a HLA-compatible embryo is combined with the detection of mutation(s) underlying immunodeficiencies and hemoglobinopathies. We report a combined retrospective and prospective cohort analysis of PGT-(M-)HLA procedures carried out from 1998 until 2017, with follow-up of transplantations to 2019. During the study period, 234 couples from 22 countries were invited for a multidisciplinary consultation. Two couples were rejected and 70 couples declined (various reasons), leaving 162 couples for which 414 clinical cycles were carried out. Cleavage stage biopsy followed by single-cell multiplex PCR for short tandem repeat-based haplotyping was applied in most cases (98.7%). The diagnostic efficiency was high (94.8%) but only 16.5% of the embryos was genetically suitable for transfer. Fresh and frozen-thawed embryo transfer resulted in 67 clinical pregnancies, 63 deliveries, and 74 live births, of which 60 children were HLA compatible. This yielded a live birth delivery rate of 30.3% per transfer. Information on neonatal characteristics of the matching PGT-(M-)HLA children showed reassuring outcomes. So far, HSCT was carried out successfully for 25 out of 26 cases. In conclusion, our data show that PGT-(M-)HLA is a valuable procedure: the high complexity and limited delivery rate are balanced by the successful HSCT outcome and the positive impact on families.

Depression, pregnancy-related anxiety and parental-antenatal attachment in couples using preimplantation genetic diagnosis.

STUDY QUESTION: Do preimplantation genetic diagnosis (PGD) couples experience higher levels of stress during pregnancy and the perinatal period compared with couples who conceive spontaneously (SC) or with ICSI? SUMMARY ANSWER: PGD couples did not experience more psychological stress during pregnancy and beyond than ICSI or SC couples. WHAT IS ALREADY KNOWN: Previous studies have shown that assisted reproduction technology (ART) couples are more prone to pregnancy-related anxieties than SC couples, but display depressed feelings to an equal or lesser extent. However, only one study has focused on a female PGD sample, which may be a more vulnerable group than other ART groups, due to the potentially complex hereditary background, adverse childhood experiences and losses. In that study, PGD women experienced a reduction in state anxiety, and maternal-antenatal attachment did not differ from normative data. Unfortunately, no data exist on pregnancy-related anxiety, depression and parental-antenatal attachment. Valuable information from both parents (e.g.: couples) is also lacking. STUDY DESIGN, SIZE, DURATION: For this longitudinal prospective study questionnaire, data from 185 women and 157 men (157 couples) were collected between February 2012 until April 2014. Data were analysed using multilevel analysis. The couples conceiving after PGD, ICSI or SC were followed from the first trimester of the pregnancy until the third month post-partum. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 60 PGD, 58 ICSI and 69 SC couples were initially recruited by various departments of Universitair Ziekenhuis Brussel (UZ Brussel). At each trimester (T1: 12-14 weeks, T2: 20-22 weeks, T3: 30-32 weeks) of pregnancy, depression (EPDS), pregnancy-related anxieties (PRAQ) and parental-antenatal attachment (M/PAAS) were recorded. At T4 (3 months post-partum), depression (EPDS) was assessed again. In the first trimester (T1) broad socio-demographic data and at T4 perinatal health data of both mother and child were recorded. Differences between conception groups over time were analysed using multilevel analyses, taking into account covariation between measurements and within couples. Several perinatal covariates as well as social desirability, coping and adult attachment style were controlled for. MAIN RESULTS AND THE ROLE OF CHANCE: All three conception groups had similar scores for depression during pregnancy and beyond. Also, pregnancy-related anxiety scales did not differ among the three groups. All groups also followed a similar trajectory in time regarding their scores for anxiety, depression and parental-antenatal attachment. ART groups did not give more socially desirable answers than SC controls. The subsequent moderators: coping and adult attachment style did not add any relevant information. No interaction effects occurred between gender and conception groups. LIMITATIONS, REASONS FOR CAUTION: The participants were Caucasian, Dutch-speaking couples, with medium to high socio-economic status, from a single centre. Our data should be replicated by multicultural and multicentre studies. Furthermore, the inclusion of an additional control group of couples who did not opt for PGD but for prenatal diagnosis may point to the most beneficial strategy for the couple. WIDER IMPLICATIONS OF THE FINDINGS: PGD parents invest a similar amount of time and emotion in their future children compared with controls. This implies that successful PGD treatment makes an important psychological contribution towards the well-being of couples given their complex hereditary and family backgrounds. STUDY FUNDING/COMPETING INTERESTS: This research project was funded by grants from the internal research council of the Vrije Universiteit Brussel (OZR), the Flemish Fonds Wetenschappelijk Onderzoek (FWO) and the Wetenschappelijk Fonds Willy Gepts (WGFG). UZ Brussel and the Centre for Medical Genetics have received several educational grants for organizing the data collection, from IBSA, Ferring, Organon, Shering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speaker's fees from Organon, Serono Symposia and Merck.

Psychosocial development of full term singletons, born after preimplantation genetic diagnosis (PGD) at preschool age and family functioning: a prospective case-controlled study and multi-informant approach.

STUDY QUESTION: Do full term singletons born after preimplantation genetic diagnosis (PGD) differ in their psychosocial functioning from children born after intracytoplasmic sperm injection (ICSI) and spontaneous conceived controls (SC)? SUMMARY ANSWER: The psychosocial maturation process of 5-6-year-old PGD children is comparable between the three conception groups (PGD, ICSI and SC). WHAT IS ALREADY KNOWN: In general, a lot of research has been published regarding follow-up of children born after artificial reproductive technologies (ART), which mainly is reassuring. But the ART population itself is marked by broad diversity [IVF, ICSI, gamete donation, preimplantation genetic screening (PGS) or PGD] which complicates comparisons. Some literature concerning the socio-emotional development of PGD/PGS children is available and it suggests a normal maturation process. However, the complex reality of PGD families (e.g. safety of the technique and psychological burden of genetic histories) asks for an exclusive PGD sample with matched control groups and a multi-informant approach. STUDY DESIGN, SIZE, DURATION: Between April 2011 and May 2013, the psychosocial wellbeing of preschoolers and their families born after PGD was assessed in a prospective case-controlled, matched follow-up study, with a multi-informant approach. PARTICIPANTS/MATERIALS, SETTING, METHODS: A group of 47 PGD, 50 ICSI and 55 SC 5-6-year-old children participated in a follow-up study performed at the Centre for Medical Genetics of the Universitair Ziekenhuis Brussel (UZ Brussel). Assessments took place in the hospital and in kindergartens. Children performed the Bene-Anthony family relations test (FRT), yielding their perceptions upon family relationships. Parents and teachers completed the child behaviour checklist (CBCL) and Caregiver Teacher Report Form (C-/TRF), respectively. Parental and family functioning were measured by the NEO-FFi, the parenting stress index (PSI), the Greenberger Work-Parenting Investment Questionnaire and the Marlowe-Crowne Social Desirability Scale (MCSDS). Statistical analysis was performed by using analysis of covariance (ANCOVA). MAIN RESULTS AND THE ROLE OF CHANCE: No differences were detected between the psychosocial development of PGD children and the control groups. Parents did not differ in reporting problem behaviour and they were stricter than teachers. Concerning family functioning the ART parents scored comparable with each other. PGD and ICSI mothers were emotionally more stable [NEO-FFi Neuroticism/emotionality: P = 0.013, η(2) = 0.066; 95% confidence interval (CI) 95% (0.003;0.148)]. They experienced less parental stress in general [PSI, Total stress: P = 0.001, η(2) = 0.102, 95% CI (0.02;0.192)] and on different sublevels opposed to their SC counterparts. Yet ART mothers presented higher ratings on the NEO-FFi Conscientiousness [P = 0.011, η(2) = 0.064; 95% CI (0.003;0.144)] indicating a higher feeling of competence and goal directedness. Mediation analysis confirmed: PGD and ICSI mothers who experienced less family stress were emotionally more stable. A power analysis indicated that a sample with 152 children is sufficient to detect a medium size effect with 80% power using ANCOVA. LIMITATIONS, REASONS FOR CAUTION: The current sample comprised only Dutch speaking Caucasians, hence conclusions should be drawn cautiously. Future research should include larger groups, prematures, multiples and children from different cultural backgrounds. WIDER IMPLICATIONS OF THE FINDINGS: This current research is the first to compare PGD preschoolers with matched controls. Concerns about the behavioural effects on the offspring should not inhibit the use of PGD. Furthermore, our findings suggest that on the long run ART procedures might enhance personal resources of women to cope with family stress. These findings are reassuring for women who might feel insecure and anxious during their ART trajectory. STUDY FUNDING/COMPETING INTERESTS: This research project gained funding from the OZR (a grant by the Research group of the Vrije Universiteit Brussel), the FWO (Fonds Wetenschappelijk Onderzoek) and the Wetenschappelijk Fonds Willy Gepts. The UZ Brussel and the Centre of Medical Genetics received funding from pharmaceutical firms for data collection. UZ Brussel and the Centre for Medical Genetics have received many educational grants for organizing the data collection, from IBSA, Ferring, Organon, Shering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speaker's fees from Organon, Serono Symposia and Merck. The other authors have no competing interests. TRIAL REGISTRATION NUMBER: not applicable.

Does oocyte banking for anticipated gamete exhaustion influence future relational and reproductive choices? A follow-up of bankers and non-bankers.

STUDY QUESTION: What is the nature of the relational status, reproductive choices and possible regret of a pioneer cohort of women that either considered or actually performed oocyte banking for anticipated gamete exhaustion (AGE)? SUMMARY ANSWER: Only half of the women who banked oocytes anticipate using them in the future but the experience with oocyte banking is overwhelmingly positive, with the majority of AGE bankers preferring to have it performed at a younger age. WHAT IS KNOWN ALREADY: Most women who choose to cryopreserve oocytes for the prevention of age-related fertility decline are single and are hoping to buy time in their search for a suitable partner. The question of why some candidates actually embark on such treatment while others eventually prefer not to freeze remains unclear. There are no follow-up data available either on post-freezing changes in relational status, or on attitude towards the undergone treatment and the reproductive outcome. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study was performed with 140 women who visited the outpatient clinic between 2009 and 2011. All women (mean age 36.7 ± SD 2.62) considered oocyte preservation for age-related infertility. At least 1 year after their initial visit (range 12-45 months), women were contacted by phone to participate in a standardized questionnaire developed to evaluate their actual relational and reproductive situation, their attitude towards banking and future reproductive plan. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eighty-six women (61.4%) completed at least one cryopreservation cycle. The non-bankers included 54 women who either preferred no treatment (n = 51) or attempted stimulation but cancelled because of poor response (n = 3). The response rate among bankers was 75.4% (65/86) while 55.8% (29/52) of the non-bankers were reached for interview. MAIN RESULTS AND THE ROLE OF CHANCE: Among bankers, 50.8% of women think they will use the oocytes at some point, while 29.2% indicated that they currently consider the use of frozen oocytes less likely than anticipated at time of oocyte retrieval. However, although 95.4% would decide to do it again, the majority (76.0%) would prefer to do it at a younger age. Among bankers, 96.1% would recommend the treatment to others. Women who banked accept a higher maximum age for motherhood when compared with non-bankers (43.6 versus 42.5 years; P < 0.05). Almost all bankers and 89.6% of the non-bankers still have a desire for a child. Bankers and non-bankers did not differ in terms of experiencing steady relations (47.7 versus 55.2%), attempting conception (35.4 versus 44.8%) and not conceiving within 1 year (17.4 versus 15.4%). LIMITATIONS, REASONS FOR CAUTION: The study has a limited follow-up of 1-3 years and therefore does not provide information on the reproductive outcome of the cryopreserved oocytes. Although most women appear to be realistic about their chances of pregnancy, the outcome of such treatment could affect the attitude of women towards the treatment. Furthermore, the findings of non-bankers cannot be generalized to the general population because the control group of non-bankers in this study actually visited a centre as a potential candidate for banking. WIDER IMPLICATIONS OF THE FINDINGS: Bankers and non-bankers have a surprising congruent relational status and reproductive choices, indicating that freezing oocytes does not appear to influence the life choices of the women. The study provides insights into the important psychological aspect of reassurance associated with preventive oocyte banking, expressed by high satisfaction after banking in combination with a decreased intention of ever using the eggs.

Cognitive and psychomotor development of 5- to 6-year-old singletons born after PGD: a prospective case-controlled matched study.

STUDY QUESTION: Do preschool preimplantation genetic diagnosis (PGD) children differ in their cognitive and psychomotor development from children born after ICSI and spontaneous conception (SC)? SUMMARY ANSWER: The cognitive development of PGD pre-schoolers was comparable to children born after ICSI and SC but motor development differed between ICSI and SC groups. STUDY DESIGN, SIZE DURATION: The cognitive abilities and motor skills of 5- to 6-year-old singletons born after PGD (n = 47) were assessed in comparison with 49 ICSI and 48 SC children in a prospective, case-controlled, matched follow-up study between April 2011 and May 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: PGD singletons, ICSI and SC children of preschool age were examined with the Wechsler Preschool and Primary Scale of Intelligence (WPSSI-III-NL) and the Movement ABC (M ABC). The WPSSI-III-NL revealed scores for Full IQ, Verbal IQ and Performance IQ. The M ABC yields a total score and comprising scores for measurements of balance, dexterity and ball skills. Since embryo biopsy is the only technical difference between the PGD and ICSI procedures, ICSI children were included as controls. These children were part of a Dutch-speaking cohort of children conceived after assisted reproduction technology (ART) at the Universitair Ziekenhuis Brussel (UZ Brussel) who received longitudinal follow-up. The SC children acted as a second control group similar to the fertile PGD sample and in contrast to the ICSI group. The SC group was recruited through announcements in a variety of media. The children were matched for age, gender, birth order and educational level of the mother. The assessments carried out for the ART groups were blinded whenever possible. The data were analysed using analysis of covariance (ANCOVA) and partial eta squared (η(2)), which was used as a measurement of effect size. MAIN RESULTS AND THE ROLE OF CHANCE: The overall cognitive development of PGD singletons did not differ from controls [P = 0.647, η(2) = 0.006; 95% confidence interval (CI) (0, 0.043)]. The partial IQ scores for Verbal and Performance intelligence revealed similar results. Analysis of motor development based on the total score as well as subscales did indicate a significant difference between the three conception groups [P = 0.033, η(2) = 0.050, 95% CI (0, 0.124)]. Post hoc analysis indicated that the significant difference was situated between performances of ICSI and SC children. Balance capacities [P = 0.004, η(2) = 0.079, 95% CI (0.025, 0.163)] and its post hoc analysis yielded equivalent results. Motor capacities of PGD singletons, however, did not differ from any of the two other conception groups. LIMITATIONS, REASONS FOR CAUTION: Given that we only assessed Caucasian singletons born after PGD, caution is required when drawing more general inferences from our results. The small sample size may be a limitation. A priori power analysis, however, revealed that at least 52 children per group were needed to detect a medium effect and 80% power using ANCOVA. Originally our sample met this threshold but we had to exclude six cases in order to remove outliers and due to missing data. WIDER IMPLICATIONS OF THE FINDINGS: Long-term follow-up of children born after embryo biopsy, in this case for PGD, is needed to confirm that the development of these children remains comparable to ICSI and SC children. Our findings do support the safety of the PGD technique and will reassure patients with hereditary genetic diseases regarding the health of their future offspring conceived with PGD. STUDY FUNDING/COMPETING INTERESTS: Funding for this study was obtained from the OZR (Research group of the Vrije Universiteit Brussel), the FWO (Fonds Wetenschappelijk Onderzoek) and the Wetenschappelijk Fonds Willy Gepts. The UZ Brussel and the Centre of Medical Genetics received funding from pharmaceutical firms for data collection. UZ Brussel and the Centre for Medical Genetics have received many educational grants for organizing the data collection, from IBSA, Ferring, Organon, Shering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speaker's fees from Organon, Serono Symposia and Merck.

A survey on the intentions and attitudes towards oocyte cryopreservation for non-medical reasons among women of reproductive age.

BACKGROUND: Although cryopreservation of semen is a routine procedure for preserving male gametes, an efficient method of preserving fertility through oocyte freezing has only recently become available for women. In view of the limited female reproductive lifespan, oocyte freezing can now offer women some protection against the decline in fertility with aging. METHODS: A survey was performed in Belgium among 1914 women of reproductive age (21-40 years) to assess public attitudes towards the phenomenon called 'social oocyte freezing'. Women were questioned on their awareness of the age-related fertility decline and their views and intentions towards considering undergoing oocyte cryopreservation. RESULTS: The electronic questionnaire was completed by 1049 women, giving a response rate of 55%, and 25 were excluded as they were incomplete/inconsistent. Our results demonstrate that 31.5% of respondents consider themselves as potential social oocyte freezers, of which 3.1% would definitely consider the procedure. Just over half of the women (51.8%) would not consider the procedure while 16.7% indicated they had no opinion. Potential oocyte freezers are characterized by a higher number of desired children and more openness to oocyte donation. The decision to actually embark on such treatment would primarily depend on conditions, such as the procedure not affecting their natural fertility and the health of future children. CONCLUSIONS: We conclude that a significant proportion of young women would consider safeguarding their reproductive potential or are at least open to the idea of social oocyte freezing.

International collaborative study of intracytoplasmic sperm injection-conceived, in vitro fertilization-conceived, and naturally conceived 5-year-old child outcomes: cognitive and motor assessments.

OBJECTIVE: To date, very few studies have been conducted on the neurodevelopmental well-being of children conceived through intracytoplasmic sperm injection (ICSI). The limitations of these studies often include a lack of comparison with a demographically matched, naturally conceived (NC) group and the investigation of only very young children, with relatively small samples sizes. One study showed that there were no differences in IQ scores among ICSI-conceived, in vitro fertilization (IVF)-conceived, and NC children at 5 years of age. Unfortunately, psychomotor development was not assessed in that study. Because findings regarding these children's cognitive and motor development are inconclusive, the aim of this study was to shed more light on the cognitive and motor development of 5-year-old ICSI-conceived children. METHODS: A total of 511 ICSI-conceived children were compared with 424 IVF-conceived children and 488 NC controls. Children were recruited in 5 European countries, ie, Belgium, Denmark, Greece, Sweden, and the United Kingdom. Participation rates ranged from 45% to 96% in the ICSI and IVF groups and from 34% to 78% in the NC group. Cognitive and motor development was assessed with the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) and McCarthy Scales of Children's Abilities (MSCA) Motor Scale, respectively. The WPPSI-R consists of 2 major scales, ie, Verbal and Performance, each including 6 subtests. The 6 Performance Scale subtests are object assembly, geometric design, block design, mazes, picture completion, and animal pegs. The 6 Verbal Scale subtests are information, comprehension, arithmetic, vocabulary, similarities, and sentences. Scores on the Performance and Verbal Scale subtests are summed to yield the performance IQ (PIQ) and verbal IQ (VIQ), respectively. Scores on both the Performance Scale and the Verbal Scale yield the full-scale IQ (FSIQ). IQ scales have a mean score of 100 and a SD of 15. Each subtest has a mean score of 10 and a SD of 3. The MSCA consists of 6 scales, ie, Verbal, Perceptual-Performance, Quantitative, General Cognitive, Memory, and Motor Scale. In this study, only the Motor Scale was administered. This scale assesses the child's coordination during performance of a variety of gross- and fine-motor tasks. Leg coordination, arm coordination, and imitative action tests provide measures of gross-motor ability. Draw-a-design and draw-a-child assess fine-motor coordination, as revealed by the levels of hand coordination and finger dexterity. The mean score for this test is 50, with a SD of . RESULTS: No differences were identified among ICSI, IVF, and NC children with respect to VIQ, PIQ, or FSIQ scores of the WPPSI-R. Furthermore, there were no differences between groups regarding the discrepancy between VIQ and PIQ scores. These results were not influenced by gender, country, or maternal educational level. However, in the subgroup of firstborn children with mothers who gave birth at an older age (33-45 years), NC children obtained significantly better VIQ and FSIQ scores than did children conceived through assisted reproductive technologies. These differences in VIQ and FSIQ scores between ICSI/IVF and NC children were relative, because NC children scored <1 IQ point higher than ICSI/IVF children. Therefore, these scores show no clinical relevance. For Verbal Scale subtests, variables such as age of the mother at the time of the birth, educational level of the mother, and gender and nationality of the child interacted with mode of conception, resulting in clinically irrelevant differences between scores for the ICSI/IVF and NC groups on the arithmetic, vocabulary, and comprehension subtests. For Performance Scale subtests, these same demographic factors interacted with mode of conception for the block design, object assembly, and animal pegs subtests, again resulting in clinically irrelevant differences among groups. In the 3 groups (ICSI, IVF, and NC), we observed equal numbers of children scoring below 1 SD from the mean on the WPPSI-R and the MSCA. CONCLUSIONS: This study includes a substantial number of children from several European countries. Apart from a few interaction effects between mode of conception and demographic variables, no differences were found when ICSI, IVF, and NC scores on the WPPSI-R and MSCA Motor Scale were compared. Nevertheless, the aforementioned interaction effects could indicate that demographic variables such as maternal age at the time of the birth and maternal educational level play different roles in the cognitive development of IVF and ICSI children, compared with NC children. Additional research is needed to explore and verify this finding. Previous studies revealed that ICSI children, in comparison with NC children, more frequently obtained scores below 1 SD from the mean on 3 subtests of the Performance Scale (object assembly, block design, and mazes) or showed a trend of 5.2% of ICSI children, compared with 2.5% of IVF children and 0.9% of NC children, obtaining a score below 1 SD from the mean, but those findings were not confirmed in this study. Here no differences were found among the 3 groups in the numbers of children scoring below 1 SD from the mean on the VIQ, PIQ, and FSIQ tests and the Verbal and Performance Scale subtests. Motor development results were somewhat more conclusive. There were no differences between the scores of ICSI, IVF, and NC children on the MCSA Motor Scale. No interaction effects were found between mode of conception and demographic variables, indicating that these results are not influenced by gender, nationality, maternal educational level, or maternal age at the time of the birth. Furthermore, equal proportions of children in all 3 groups scored below 1 SD from the mean. The results of this study are reassuring for parents who conceived through ICSI (or IVF). The findings indicate that the motor and cognitive development of their offspring is very similar to that of NC children. However, demographic factors such as maternal educational level and maternal age at the time of the birth might play different roles in the cognitive development of ICSI and IVF children, compared with NC children.

Psychological follow-up study of 5-year-old ICSI children.

BACKGROUND: The developmental outcomes of children born after ICSI are still a matter of concern. The purpose of the present study was to investigate psychological outcomes for 5-year-old children born after ICSI and compare these with outcomes for children born after spontaneous conception (SC). METHODS: Three hundred singleton children born after ICSI in Belgium, Sweden and the USA were matched by maternal age, child age and gender. Outcome measures included the Wechsler Preschool and Primary scales of intelligence (WPPSI-R), Peabody Developmental Motor Scales, Parenting Stress Index and Child Behaviour Checklist. RESULTS: Regarding cognitive development, no significant differences were found on WPPSI-R verbal and performance scales between ICSI and SC children. However, some differences were noted on subtests of the Performance Scale. ICSI children more often obtained a score below 1 SD of the mean on the subtests: Object Assembly, Block Design and Mazes (all P<0.05). Significant differences by site (i.e. Belgium, Sweden and New York) were found on subtests related to parenting stress, child behaviour problems and motor development (all P<0.05). These findings can probably be explained by variables other than conception mode, such as cultural differences and selection bias. CONCLUSIONS: Although the finding that a higher proportion of ICSI children obtained scores below the cut-off on some of the visual-spatial subscales of the WPPSI-R warrants further investigation, ICSI does not appear to affect the psychological well-being or cognitive development at age 5.

The influence of assisted reproduction on family functioning and children's socio-emotional development: results from a European study.

BACKGROUND: ICSI is used with increasing frequency, but there is less information about the children born following this method of assisted reproduction than other forms of IVF. Some authors have suggested that it may contribute to more family stress than IVF. METHODS: ICSI conceived children were compared with IVF conceived children and naturally conceived (NC) controls. They were selected in five European countries: Belgium, Denmark, Greece, Sweden and the UK, and seen for psychological testing and a paediatric examination when they were 5 years old. In all countries, except Greece, mothers and fathers were asked to complete questionnaires about parental well-being, family relationships, parenting and child behaviour. RESULTS: Very few differences were found between the ICSI and NC group or the ICSI and IVF group. The only significant differences were that mothers in the ICSI conceived group reported fewer hostile or aggressive feelings towards the child and higher levels of commitment to parenting than the mothers of NC children. CONCLUSIONS: The study confirms the results of previous work with IVF families. This should be encouraging for families using these techniques in the future.