Health of singletons born after frozen embryo transfer until early adulthood : a Finnish register study

STUDY QUESTION Is the health of singletons born after frozen embryo transfer (FET) comparable to that of singletons born after fresh embryo transfer (ET) until early adulthood? SUMMARY ANSWER The health of singletons born after FET does not differ from that of singletons born after fresh ET. WHAT IS KNOWN ALREADY The differences in perinatal outcomes of children born after FET and fresh ET are well known. FET is associated with an increased risk of large-for-gestational-age but diminished risks of preterm birth (PTB), small-for-gestational-age and decreased perinatal mortality compared to fresh ET. However, knowledge on the long-term health after FET is scarce. STUDY DESIGN, SIZE, DURATION This retrospective register-based cohort study compares singletons born after FET (n = 1825) between the years 1995 and 2006 to those born after fresh ET (n = 2933) and natural conception (NC, n = 31 136) with a mean follow-up time of 18-20 years. PARTICIPANTS/MATERIALS, SETTING, METHODS Singletons born after FET were compared to those born after fresh ET and NC regarding the frequencies of diagnoses in the main ICD-10 chapters (International Statistical Classification of Diseases and Related Health Problems, 10th revision), the number of outpatient visits and hospital admissions, and mortality. Adjustments were made for PTB, maternal age, parity, socioeconomic status based on mother's occupation and offspring sex. The study combines data from the Finnish Medical Birth Register, the Finnish Care Register for Health Care (CRHC) and the Cause-of-Death Register at Statistics Finland. The Student's T-test was used for continuous variables, and the Chi-square test was used for categorical variables. Cox regression was used to estimate crude and adjusted hazard ratios (HRs and aHRs, respectively). A general linear model was used to compare the means of outpatient visits, hospital admissions and lengths of hospital stays per person. MAIN RESULTS AND THE ROLE OF CHANCE No significant differences between the FET and fresh ET groups were found in the frequency of diagnoses in any of the ICD-10 chapters or in the parameters describing the need for hospital care. However, compared to the NC group, higher proportions in the FET group had outpatient visits in the hospital (93.5% vs 92.2%, aHR 1.23, 95% CI 1.17, 1.30) or hospital admissions (48% vs 46.5%, aHR 1.28, 95% CI 1.19, 1.37). Compared to the NC group, the FET group had elevated adjusted risks of diagnoses of infectious and parasitic diseases (aHR 1.24; 95% CI 1.11, 1.38), neoplasms (aHR 1.68; 95% CI 1.48, 1.91), diseases of the eye and adnexa, the ear or mastoid process (aHR 1.11; 95% CI 1.01, 1.21), the respiratory system (aHR 1.15; 95% CI 1.06, 1.23), the digestive system (aHR 1.17; 95% CI 1.05, 1.32), the skin or subcutaneous tissue (aHR 1.28; 95% CI 1.14, 1.43) and the genitourinary system (aHR 1.27; 95% CI 1.11, 1.45), as well as congenital malformations or chromosomal abnormalities (aHR 1.31; 95% CI 1.14, 1.50) and symptoms, signs or abnormal clinical or laboratory findings (aHR 1.25, 95% CI 1.16, 1.34). LIMITATIONS, REASONS FOR CAUTION Only hospital-based inpatient and outpatient care is covered by the CRHC register, excluding milder cases diagnosed elsewhere. We were not able to study the effect of ART treatments and subfertility separately in our setting. In addition, although our cohort is reasonably sized, even larger cohorts would be needed to reliably study rare outcomes, such as cancer. WIDER IMPLICATIONS OF THE FINDINGS For many ICD-10 chapters, we present the first published data on the long-term outcome of singletons born after FET. The results on FET versus fresh ET are reassuring, whereas the results on FET versus NC warrant further investigation. STUDY FUNDING/COMPETING INTEREST(S) Finnish government research funding was obtained for this study. Funding was also obtained from the Finnish Medical Society Duodecim, the Paivikki and Sakari Sohlberg Foundation, Orion Research Foundation, Finnish Society of Obstetrics and Gynaecology (research grants to A.M.T.) and Finnish government research funding. The funding sources were not involved in the planning or execution of the study. The authors have no competing interests to declare.Peer reviewe

Growth of singletons born after frozen embryo transfer until early adulthood: a Finnish register study

Abstract STUDY QUESTION: Are there growth differences between singleton children born after frozen embryo transfer (FET), fresh embryo transfer (ET), and natural conception (NC)? SUMMARY ANSWER: Adolescent boys born after FET have a higher mean proportion and increased odds of overweight compared to those born after fresh ET. WHAT IS KNOWN ALREADY: Children born after FET have higher mean birthweights and an increased risk of large-for-gestational-age compared to those born after fresh ET and even NC. This raises questions about possible growth differences later in childhood. Previous studies on child growth after FET report partly conflicting results and lack long-term data until adolescence. STUDY DESIGN, SIZE, DURATION: This was a cohort study based on national population-based registers, the Finnish Medical Birth Register and the Register of Primary Health Care visits, including singletons born after FET (n = 1825), fresh ET (n = 2933), and NC (n = 31 136) in Finland between the years 1995 and 2006. PARTICIPANTS/MATERIALS, SETTING, METHODS: The proportions of overweight (i.e. age- and sex-adjusted ISO-BMI for children ≥ 25) were compared between the groups. Odds ratios (ORs) and adjusted odds ratios (aORs) of overweight were calculated. Adjustments were made for birth year, preterm birth, maternal age, parity, and socioeconomic status. Mean heights, weights, and BMIs were compared between the groups each year between the ages of 7 and 18. MAIN RESULTS AND THE ROLE OF CHANCE: FET boys had a higher mean proportion of overweight (28%) compared to fresh ET (22%, P < 0.001) and NC (26%, P = 0.014) boys. For all ages combined, the aOR of overweight was increased (1.14, 95% CI 1.02–1.27) for FET boys compared to fresh ET boys. For girls, the mean proportions of overweight were 18%, 19%, and 22% for those born after FET, fresh ET, and NC, respectively (P = 0.169 for FET vs fresh ET, P < 0.001 for FET vs NC). For all ages combined, FET girls had a decreased aOR of overweight (0.89, 95% CI 0.80–0.99) compared to NC girls. Growth measurements were available for 6.9% to 30.6% of FET boys and for 4.7% to 29.4% of FET girls at different ages. LIMITATIONS, REASONS FOR CAUTION: Unfortunately, we were not able to adjust for parental anthropometric characteristics. The growth data were not available for the whole cohort, and the proportion of children with available measurements was limited at the start and end of the follow-up. During the study period, mainly cleavage stage embryos were transferred, and slow freezing was used for ART. WIDER IMPLICATIONS OF THE FINDINGS: The risk of overweight among FET boys warrants further research. Future studies should aim to investigate the mechanisms that explain this sex-specific finding and combine growth data with long-term health data to explore the possible risks of overweight and cardiometabolic disease in adulthood. STUDY FUNDING/COMPETING INTEREST(S): Funding was obtained from the Päivikki and Sakari Sohlberg Foundation, the Alma and K.A. Snellman Foundation (personal grants to A.M.T.), and the Finnish Government Research Funding. The funding sources were not involved in the planning or execution of the study. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.Abstract STUDY QUESTION: Are there growth differences between singleton children born after frozen embryo transfer (FET), fresh embryo transfer (ET), and natural conception (NC)? SUMMARY ANSWER: Adolescent boys born after FET have a higher mean proportion and increased odds of overweight compared to those born after fresh ET. WHAT IS KNOWN ALREADY: Children born after FET have higher mean birthweights and an increased risk of large-for-gestational-age compared to those born after fresh ET and even NC. This raises questions about possible growth differences later in childhood. Previous studies on child growth after FET report partly conflicting results and lack long-term data until adolescence. STUDY DESIGN, SIZE, DURATION: This was a cohort study based on national population-based registers, the Finnish Medical Birth Register and the Register of Primary Health Care visits, including singletons born after FET (n = 1825), fresh ET (n = 2933), and NC (n = 31 136) in Finland between the years 1995 and 2006. PARTICIPANTS/MATERIALS, SETTING, METHODS: The proportions of overweight (i.e. age- and sex-adjusted ISO-BMI for children ≥ 25) were compared between the groups. Odds ratios (ORs) and adjusted odds ratios (aORs) of overweight were calculated. Adjustments were made for birth year, preterm birth, maternal age, parity, and socioeconomic status. Mean heights, weights, and BMIs were compared between the groups each year between the ages of 7 and 18. MAIN RESULTS AND THE ROLE OF CHANCE: FET boys had a higher mean proportion of overweight (28%) compared to fresh ET (22%, P < 0.001) and NC (26%, P = 0.014) boys. For all ages combined, the aOR of overweight was increased (1.14, 95% CI 1.02–1.27) for FET boys compared to fresh ET boys. For girls, the mean proportions of overweight were 18%, 19%, and 22% for those born after FET, fresh ET, and NC, respectively (P = 0.169 for FET vs fresh ET, P < 0.001 for FET vs NC). For all ages combined, FET girls had a decreased aOR of overweight (0.89, 95% CI 0.80–0.99) compared to NC girls. Growth measurements were available for 6.9% to 30.6% of FET boys and for 4.7% to 29.4% of FET girls at different ages. LIMITATIONS, REASONS FOR CAUTION: Unfortunately, we were not able to adjust for parental anthropometric characteristics. The growth data were not available for the whole cohort, and the proportion of children with available measurements was limited at the start and end of the follow-up. During the study period, mainly cleavage stage embryos were transferred, and slow freezing was used for ART. WIDER IMPLICATIONS OF THE FINDINGS: The risk of overweight among FET boys warrants further research. Future studies should aim to investigate the mechanisms that explain this sex-specific finding and combine growth data with long-term health data to explore the possible risks of overweight and cardiometabolic disease in adulthood. STUDY FUNDING/COMPETING INTEREST(S): Funding was obtained from the Päivikki and Sakari Sohlberg Foundation, the Alma and K.A. Snellman Foundation (personal grants to A.M.T.), and the Finnish Government Research Funding. The funding sources were not involved in the planning or execution of the study. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A

C-reactive protein response is higher in early than in late ovarian hyperstimulation syndrome

Objectives: Many in vitro fertilization (IVF) complications are inflammatory by nature, some of which are even life-threatening. We evaluated the response of C-reactive protein (CRP) in IVF complications, especially in early and late ovarian hyperstimulation syndrome (OHSS), to support clinical decision making in gynecological emergency policlinics. Study design: In a prospective two-year study at Helsinki University Hospital, Finland, we recruited patients with IVF complications including moderate or severe OHSS (n = 47 patients: 36 early and 14 late OHSS cases), or other IVF complications (n = 13). As controls, we recruited women in an uncomplicated IVF cycle (n = 27). Serial blood samples (CRP, blood count, platelets, albumin, estradiol, creatinine, and electrolytes) were collected from patients upon admission to the emergency polyclinic and during and after treatment on the ward, and from the controls prior, during, and after the IVF protocol. All samples were categorized according to oocyte pick-up (OPU). The statistics included comparisons between and within the study groups, and receiver-operating characteristic (ROC) curve analysis for diagnostic accuracy of CRP for early OHSS at emergency polyclinics. Results: On admission, CRP did not differentiate OHSS from other IVF complications, but CRP was higher in early (median 21; IQR 8-33 mg/L) than in late (6; 3-9 mg/L, p = 0.001) OHSS. In ROC analysis for CRP (12 mg/L), the area under the curve (AUC) was 0.74 (p = 0.001) with sensitivity of 69% and specificity of 71% for early OHSS. CRP was significantly higher (28; 10-46 mg/L) in patients with early OHSS two days after oocyte pick-up (OPU) than in the controls (5; Conclusions: Early OHSS associates with a distinct rise in CRP level beyond that induced by uncomplicated oocyte pick-up, whereas the CRP levels in late OHSS are comparable to those in the control cycles. CRP identifies, but cannot distinguish IVF complications. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

High birth weight and large-for-gestational-age in singletons born after frozen compared to fresh embryo transfer, by gestational week : a Nordic register study from the CoNARTaS group

AbstractSTUDY QUESTION: When do the differences in birth weights become apparent between singletons born after frozen embryo transfer (FET) and fresh embryo transfer (fresh ET)?SUMMARY ANSWER: Mean birth weights after FET become significantly higher starting from gestational week (GW) 33 among boys and from GW 34 among girls.WHAT IS KNOWN ALREADY: In recent years, there has been a steep rise in recorded FET treatments, enabling widespread use of elective single embryo transfer, thus reducing the risks associated with multiple gestations. However, singletons born after FET are heavier and there is a higher risk of large-for-gestational-age (LGA) (birth weight > 90 percentiles) compared to fresh ET. In contrast, risk of small-for-gestational-age (SGA, birth weight STUDY DESIGN, SIZE, DURATION: This retrospective Nordic register-based cohort study compared singletons born after FET (n = 17 500) to singletons born after fresh ET (n = 69 510) and natural conception (NC, n = 3 311 588). All live born singletons born between the years 2000 and 2015 in Denmark, Norway and Sweden at gestational age ≥22 weeks were included from the population-based Committee of Nordic ART and Safety (CoNARTaS) study population.PARTICIPANTS/MATERIALS, SETTING, METHODS: Children born after FET were compared to those born after fresh ET and NC for mean birth weight and proportion of LGA and SGA for each GW at birth. Chi-square test and tests for relative proportions were used to compare categorical variables and Student’s t-test was used to compare continuous variables. Adjusted odds ratios (aORs) for LGA and SGA were calculated using logistic regressions, adjusting for year of birth, maternal age, parity, BMI, chronic hypertension, diabetes, smoking and offspring sex.MAIN RESULTS AND THE ROLE OF CHANCE: Mean birth weights were significantly higher after FET compared to fresh ET starting from GW 33 (range from 75 g to 228 g by week) for boys and starting from GW 34 (range from 90 g to 236 g by week) for girls. Boys born after FET had a significantly higher proportion of LGA (11.0–15.1%) at birth between GW 36 and 42, compared to those born after fresh ET (7.1–9.4%) (range from P P = 0.048 by week). For girls born after FET, the difference was seen between GW 37 and 42 (10.6–13.4%) compared to those born after fresh ET (6.6–8.0%) (range from P The proportion of SGA was significantly lower among boys born after FET (7.6–8.7%) compared to fresh ET (11.9–13.6%) between GW 36 and 42 (range from P P = 0.016 by week). For girls born after FET, the difference was seen between GW 38 and 42 (7.0–9.3%) compared to those born after fresh ET (13.0–14.6%) (P P P P = 0.018 by week), compared to naturally conceived boys (9.7–9.9%) and girls (9.0–10.0%). All singletons born after FET had a higher risk of LGA compared to singletons born after fresh ET (aOR 1.87, 95% CI 1.76–1.98) and singletons born after NC (aOR 1.28, 95% CI 1.22–1.35).LIMITATIONS, REASONS FOR CAUTION: There may be residual confounding factors that we were not able to control for, most importantly the causes of preterm birth, which may also influence foetal growth. A further limitation is that we have no knowledge on growth patterns between implantation and GW 22. Finally, the number of children born extremely preterm or post-term was limited even in this large study population.WIDER IMPLICATIONS OF THE FINDINGS: This is, to date, the largest study on birth weights among preterm and term ART singletons with a population-based design and NC control group. The results suggest that the freeze–thaw process is associated with higher birthweights and greater risk of LGA at least in the last trimester of pregnancy. This is an important aspect of the safety profile of ART. More research is needed on the long-term outcome of these children.Abstract STUDY QUESTION: When do the differences in birth weights become apparent between singletons born after frozen embryo transfer (FET) and fresh embryo transfer (fresh ET)? SUMMARY ANSWER: Mean birth weights after FET become significantly higher starting from gestational week (GW) 33 among boys and from GW 34 among girls. WHAT IS KNOWN ALREADY: In recent years, there has been a steep rise in recorded FET treatments, enabling widespread use of elective single embryo transfer, thus reducing the risks associated with multiple gestations. However, singletons born after FET are heavier and there is a higher risk of large-for-gestational-age (LGA) (birth weight > 90 percentiles) compared to fresh ET. In contrast, risk of small-for-gestational-age (SGA, birth weight < 10 percentiles) is lower in singletons born after FET compared to fresh ET. The reasons, timing and consequences of these differences remain largely unclear. There is limited evidence about whether this difference in growth develops before the last trimester of pregnancy. STUDY DESIGN, SIZE, DURATION: This retrospective Nordic register-based cohort study compared singletons born after FET (n = 17 500) to singletons born after fresh ET (n = 69 510) and natural conception (NC, n = 3 311 588). All live born singletons born between the years 2000 and 2015 in Denmark, Norway and Sweden at gestational age ≥22 weeks were included from the population-based Committee of Nordic ART and Safety (CoNARTaS) study population. PARTICIPANTS/MATERIALS, SETTING, METHODS: Children born after FET were compared to those born after fresh ET and NC for mean birth weight and proportion of LGA and SGA for each GW at birth. Chi-square test and tests for relative proportions were used to compare categorical variables and Student’s t-test was used to compare continuous variables. Adjusted odds ratios (aORs) for LGA and SGA were calculated using logistic regressions, adjusting for year of birth, maternal age, parity, BMI, chronic hypertension, diabetes, smoking and offspring sex. MAIN RESULTS AND THE ROLE OF CHANCE: Mean birth weights were significantly higher after FET compared to fresh ET starting from GW 33 (range from 75 g to 228 g by week) for boys and starting from GW 34 (range from 90 g to 236 g by week) for girls. Boys born after FET had a significantly higher proportion of LGA (11.0–15.1%) at birth between GW 36 and 42, compared to those born after fresh ET (7.1–9.4%) (range from P < 0.001 to P = 0.048 by week). For girls born after FET, the difference was seen between GW 37 and 42 (10.6–13.4%) compared to those born after fresh ET (6.6–8.0%) (range from P < 0.001 to P = 0.009 by week). The proportion of SGA was significantly lower among boys born after FET (7.6–8.7%) compared to fresh ET (11.9–13.6%) between GW 36 and 42 (range from P < 0.001 to P = 0.016 by week). For girls born after FET, the difference was seen between GW 38 and 42 (7.0–9.3%) compared to those born after fresh ET (13.0–14.6%) (P < 0.001). The proportion of LGA (12.3–15.1%) was significantly higher for boys born after FET between GW 38 and 41 (P < 0.001) and for girls born after FET (12.6–13.4%) between GW 37 and 40 (range from P < 0.001 to P = 0.018 by week), compared to naturally conceived boys (9.7–9.9%) and girls (9.0–10.0%). All singletons born after FET had a higher risk of LGA compared to singletons born after fresh ET (aOR 1.87, 95% CI 1.76–1.98) and singletons born after NC (aOR 1.28, 95% CI 1.22–1.35). LIMITATIONS, REASONS FOR CAUTION: There may be residual confounding factors that we were not able to control for, most importantly the causes of preterm birth, which may also influence foetal growth. A further limitation is that we have no knowledge on growth patterns between implantation and GW 22. Finally, the number of children born extremely preterm or post-term was limited even in this large study population. WIDER IMPLICATIONS OF THE FINDINGS: This is, to date, the largest study on birth weights among preterm and term ART singletons with a population-based design and NC control group. The results suggest that the freeze–thaw process is associated with higher birthweights and greater risk of LGA at least in the last trimester of pregnancy. This is an important aspect of the safety profile of ART. More research is needed on the long-term outcome of these children

MMN and Differential Waveform

A mismatch negativity response (MMN) and a new differential waveform were derived in an effort to evaluate a neural refractory or recovery effect in adult listeners. The MMN was elicited using oddball test runs in which the standard and deviant stimuli differed in frequency. To derive the differential waveform, the same standard and deviant stimuli were presented alone. MMN responses were obtained by subtracting the averaged responses to standards from the deviants. The differential waveforms were obtained by subtracting the averaged responses to standards presented alone from deviants presented alone. Scalp topography for the MMN and differential waveforms were similar. A significant (p < .05) positive and negative correlation was found between the earlier and later components of the bimodal MMN and the N1 and P2 component of the differential waveform, respectively. Further, N1 and P2 of the differential waveform were significant (p < .05) predictor variables of early and late peak amplitudes of the MMN. These results suggest that refractory effects may overlay/modify the morphology of the MMN waveform

Adolescent attachment to parents and peers in singletons and twins born with assisted and natural conception

STUDY QUESTION Does adolescent attachment to parents and peers differ between singletons and twins born with ART or natural conception (NC)? SUMMARY ANSWER Adolescent attachment anxiety with the father was higher among NC singletons than among ART and NC twins, whereas attachment avoidance with the father was higher in ART singletons than in NC singletons and NC twins. No differences were found in attachment to the mother, best friend or romantic partner. WHAT IS KNOWN ALREADY Most studies have not found differences between ART and NC singletons in parent-adolescent relationships, but twin relationships may be more at risk. No previous study has examined all four groups in the same study, or specifically looked at attachment relationships. STUDY DESIGN, SIZE, DURATION This was an 18-year, prospective and controlled longitudinal study with families of 496 ART singletons, 101 ART twin pairs, 476 NC singletons and 22 NC twin pairs. Families were recruited during the second trimester of pregnancy; the ART group was recruited from five infertility clinics in Finland and the control group was recruited from a hospital outpatient clinic during a routine visit. PARTICIPANTS/MATERIALS, SETTING, METHODS Mothers and fathers gave background information for this study during pregnancy, and during the child's first year and early school age (7-8 years). For the ART group, infertility characteristics and prenatal medical information was also obtained from the patient registry of the infertility clinics. Children (originally 50% girls) filled in electronic questionnaires related to their attachment to mother, father, best friend and romantic partner (Experiences in Close Relationships-Relationship Structures) at 17-19 years of age. MAIN RESULTS AND THE ROLE OF CHANCE Adolescent attachment anxiety to father was higher in NC singletons than in ART twins, P = 0.004 and marginally higher than in NC twins, P = 0.06. Adolescent attachment avoidance to father was higher in ART singletons than in NC singletons, P = 0.006 and marginally higher than in NC twins, P = 0.055. LIMITATIONS, REASONS FOR CAUTION The sample size was small especially in the NC twin group and there was drop-out over the 18-year time period, especially among boys and families with lower parental education level. The study only included native Finnish-speaking families. The results could differ in a more diverse population. ART singletons were younger and had fewer siblings than ART twins and NC children, and ART and NC twins had more newborn health risks than ART and NC singletons. WIDER IMPLICATIONS OF THE FINDINGS The study adds to a growing body of evidence that neither ART treatments nor being a twin places mother-child relationships or peer relationships at long-term risk. However, in our study, which was the first to examine both ART and twinhood simultaneously, we found that there may be more problems in father-adolescent relationships, but only in ART singletons and only related to attachment avoidance. Our findings suggest that men, as well as women, should receive enough support in pre- and peri-natal health care during and after infertility treatments. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Academy of Finland (grant number 2501308988), the Juho Vainio Foundation and the Finnish Cultural Foundation. The authors report no conflict of interest.Peer reviewe

Top-quality embryo transfer is associated with lower odds of ectopic pregnancy

Introduction The incidence of ectopic pregnancy is up to four times higher after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) than in spontaneous pregnancies, and the risk of ectopic pregnancy is increased by tubal factor infertility and the transfer of multiple embryos. However, the effect of embryo quality on the probability of ectopic pregnancy has not been investigated until now and it is not clear whether ovarian stimulation parameters affect the incidence of ectopic pregnancy. Material and Methods An historical cohort study of 15 006 clinical pregnancies (diagnosed by ultrasound at 6-8 gestational weeks) after non-donor IVF/ICSI with fresh embryo transfer (n = 8952) or frozen-thawed embryo transfer (n = 6054). Treatments were performed during 2000-2017 in Finland. A total of 9207 (61.4%) single and 5799 (38.6%) double embryo transfers of no more than one top-quality embryo were evaluated. We analyzed the effects of multiple factors on ectopic pregnancy by logistic regression, including type of cycle (fresh vs. frozen embryo transfer), female age, number and quality of embryos transferred, tubal factor infertility and factors of ovarian response to gonadotropin stimulation. Results Ectopic pregnancy was observed in 2.3% of cycles. There was no significant difference in ectopic pregnancy rate after fresh embryo transfer and frozen embryo transfer (2.2% vs. 2.4%, p = 0.3). The ectopic pregnancy rate was lower in cycles with top-quality embryo transfer (1.9%) than of those where only non-top quality embryos were transferred (2.7%, p < 0.0001). Tubal factor infertility was diagnosed more often in ectopic pregnancy than in intrauterine pregnancies (21.2% vs. 11.0%, p < 0.0001). Logistic regression revealed lower odds for ectopic pregnancy after a top-quality embryo transfer than after transfer of a non-top quality embryo (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.56-0.92, p = 0.007). Transfer of two vs. one embryo (OR 1.35, 95% CI 1.05-1.70, p = 0.02) and tubal factor infertility (OR 2.21, 95% CI 1.68-2.91, p < 0.0001) significantly increased the risk of ectopic pregnancy. Conclusions Transfer of non-top quality embryos is associated with a higher rate of ectopic pregnancy. This is particularly important to keep in mind in treatments with only non-top embryos available even in the absence of tubal factor infertility. To minimize the risk of ectopic pregnancy, the number of embryos transferred should be as low as possible.Peer reviewe

Total stimulation gonadotropin dose per oocyte retrieved and fresh embryo quality affect live birth rate after frozen-thawed embryo transfer

Koeputkihedelmöityshoidoissa (IVF) ja munasolujen mikroinjektiohoidoissa (ICSI) elävän lapsen syntymisen todennäköisyyteen vaikuttavia tekijöitä ovat muun muassa kerättyjen munasolujen lukumäärä, saatu gonadotropiinihormonin (FSH) annos sekä luotujen korkealaatuisten alkioiden määrä. Tämän tutkimuksen tarkoituksena oli selvittää, mitkä ominaisuudet alkion tuoresiirtovaiheessa vaikuttavat syntymän todennäköisyyteen jatkossa, jos naiselle tehdään myöhemmin hedelmöityshoidossa pakastetun alkion siirto. Tutkimusaineistona oli yhteinen Suomen lapsettomuusklinikoista kerätty tietokanta, joka sisälsi tiedot yhteensä 9465 pakastusalkionsiirto-tyyppisestä hedelmöityshoidosta vuosilta 2000-2017. Tuorealkionsiirtoja tutkittiin verraten näitä samojen naisten myöhempiin pakastealkionsiirtoihin. Luteaalisen kierron hormonaalista tukea sai naisista 42.9 %, hormonaalisesti indusoitu kuukautiskierto ja ovulaatio oli 40.7 % naisista, ja 16.1 % naisista kuukautiskierto oli täysin spontaani. FSH-annosta/munasolu käytettiin munasarjojen vasteen arviointiin. Tutkimuksessa selvisi, että vertailussa matalin FSH/munasolu -annossuhde <200 IU/munasolu sai aikaan suurimman todennäköisyyden elävän lapsen syntymälle pakastealkionsiirron jälkeen. Korkeampi annossuhde 300-399 IU/munasolu sen sijaan laski merkittävästi tätä todennäköisyyttä. Potilaan hormonaalisesti indusoitu ovulaatiokierto niin ikään assosioitui matalampaan syntymän todennäköisyyteen kuin kierto, jossa oli annettu hormonaalista tukea vain luteaalivaiheessa. Mikäli ainakin yksi korkealaatuinen alkio oli saatavilla hoitojen alussa, oli syntymän todennäköisyys suurempi läpi koko prosessin. Naisen yli 35 vuoden ikä laski syntymän todennäköisyyttä. Hedelmöityshoidoissa FSH/munasolu-annossuhde kuvastaa mahdollisesti munasarjojen toimintaa ja munasolujen laatua. Annossuhde tulisi pyrkiä pitämään mahdollisimman alhaisena, jotta vältytään korkeampiin annoksiin liittyvältä syntymän todennäköisyyden laskulta

Hormone profiling, including anti-Mullerian hormone (AMH), for the diagnosis of polycystic ovary syndrome (PCOS) and characterization of PCOS phenotypes

Objective was to evaluate serum anti-Mullerian hormone (AMH) levels in polycystic ovary syndrome (PCOS) and in its different phenotypes in relation to clinical, endocrine and metabolic parameters using a new automated VIDAS((R)) method and to compare it with the Gen II method. Study design was multi-center study including 319 PCOS women and 109 healthy controls. Serum AMH levels measured using VIDAS((R)) were significantly higher in PCOS women than controls (pPeer reviewe