Background: Due to the “flare effect” associated with the flare protocol, variation in the degree of follicular maturation during stimulation may result in differences in follicle response as compared to the luteal protocol which is based on maximal pituitary suppression and synchronization of follicular maturation. In this study, besides other methods, Anti-Mullerian Hormone (AMH), a novel marker for ovarian reserve, was used as a tool to evaluate the ovarian responsiveness to stimulation. Methods: Women undergoing IVF/ICSI treatment in the UBC IVF Program from January to December 2006 using luteal and flare protocols were retrospectively selected for a total of 40 treatment cycles, 20 cycles in each protocol matched by age, weight, and indication for IVF/ICSI. Serial serum Estradiol (E₂) levels and follicle data were obtained from the clinic chart. Follicle stimulating hormone (FSH), Luteinizing Hormone (LH), progesterone (P), androstenedione (D₄) and AMH levels were measured from aliquots of frozen serum samples. Hormone responses were evaluated by Area Under the Curve (AUC). Data were analyzed using the t-test and statistical significance was considered present at P<0.05. Results are reported as the mean ± SEM. Results: For flare versus luteal protocol, there was a significant difference in the number of total follicles (14.5 ± 1.8 vs 21.3 ± 2.3), medium follicles (3.7 ± 0.6 vs 8.4 ± 1.3), eggs retrieved (8 ± 0.8 vs 14 ± 1.4) and oocytes fertilized (4.4 ± 0.5 vs 8.4 ± 0.7), AMH AUC (62 ± 12 vs 111 ± 13), LH AUC (67 ± 21 vs 20 ± 9), FSH AUC (171 ± 59 vs 112 ± 29), respectively. Mean number of embryos transferred in both groups was similar. Number of pregnancies conceived (5 for flare and 10 for luteal protocol) was not significantly different. Although E₂ AUC in luteal protocol was higher than that in flare protocol, the difference was not statistically significant (28,339 ± 2,669 vs 26,905 ± 2,790). Differences in P and D₄ AUC between the two protocols were not statistically significant. Correlations with ovarian follicles and eggs retrieved were better for AMH than E₂. Conclusions: The luteal protocol exhibited a better ovarian response to stimulation as compared to the flare protocol. As compared to E₂, AMH had a better correlation with the number of follicles and eggs retrieved.

No description available.

Background: Due to the “flare effect” associated with the flare protocol, variation in the degree of follicular maturation during stimulation may result in differences in follicle response as compared to the luteal protocol which is based on maximal pituitary suppression and synchronization of follicular maturation. In this study, besides other methods, Anti-Mullerian Hormone (AMH), a novel marker for ovarian reserve, was used as a tool to evaluate the ovarian responsiveness to stimulation. Methods: Women undergoing IVF/ICSI treatment in the UBC IVF Program from January to December 2006 using luteal and flare protocols were retrospectively selected for a total of 40 treatment cycles, 20 cycles in each protocol matched by age, weight, and indication for IVF/ICSI. Serial serum Estradiol (E₂) levels and follicle data were obtained from the clinic chart. Follicle stimulating hormone (FSH), Luteinizing Hormone (LH), progesterone (P), androstenedione (D₄) and AMH levels were measured from aliquots of frozen serum samples. Hormone responses were evaluated by Area Under the Curve (AUC). Data were analyzed using the t-test and statistical significance was considered present at P<0.05. Results are reported as the mean ± SEM. Results: For flare versus luteal protocol, there was a significant difference in the number of total follicles (14.5 ± 1.8 vs 21.3 ± 2.3), medium follicles (3.7 ± 0.6 vs 8.4 ± 1.3), eggs retrieved (8 ± 0.8 vs 14 ± 1.4) and oocytes fertilized (4.4 ± 0.5 vs 8.4 ± 0.7), AMH AUC (62 ± 12 vs 111 ± 13), LH AUC (67 ± 21 vs 20 ± 9), FSH AUC (171 ± 59 vs 112 ± 29), respectively. Mean number of embryos transferred in both groups was similar. Number of pregnancies conceived (5 for flare and 10 for luteal protocol) was not significantly different. Although E₂ AUC in luteal protocol was higher than that in flare protocol, the difference was not statistically significant (28,339 ± 2,669 vs 26,905 ± 2,790). Differences in P and D₄ AUC between the two protocols were not statistically significant. Correlations with ovarian follicles and eggs retrieved were better for AMH than E₂. Conclusions: The luteal protocol exhibited a better ovarian response to stimulation as compared to the flare protocol. As compared to E₂, AMH had a better correlation with the number of follicles and eggs retrieved.

Background: Due to the “flare effect” associated with the flare protocol, variation in the degree of follicular maturation during stimulation may result in differences in follicle response as compared to the luteal protocol which is based on maximal pituitary suppression and synchronization of follicular maturation. In this study, besides other methods, Anti-Mullerian Hormone (AMH), a novel marker for ovarian reserve, was used as a tool to evaluate the ovarian responsiveness to stimulation. Methods: Women undergoing IVF/ICSI treatment in the UBC IVF Program from January to December 2006 using luteal and flare protocols were retrospectively selected for a total of 40 treatment cycles, 20 cycles in each protocol matched by age, weight, and indication for IVF/ICSI. Serial serum Estradiol (E₂) levels and follicle data were obtained from the clinic chart. Follicle stimulating hormone (FSH), Luteinizing Hormone (LH), progesterone (P), androstenedione (D₄) and AMH levels were measured from aliquots of frozen serum samples. Hormone responses were evaluated by Area Under the Curve (AUC). Data were analyzed using the t-test and statistical significance was considered present at P<0.05. Results are reported as the mean ± SEM. Results: For flare versus luteal protocol, there was a significant difference in the number of total follicles (14.5 ± 1.8 vs 21.3 ± 2.3), medium follicles (3.7 ± 0.6 vs 8.4 ± 1.3), eggs retrieved (8 ± 0.8 vs 14 ± 1.4) and oocytes fertilized (4.4 ± 0.5 vs 8.4 ± 0.7), AMH AUC (62 ± 12 vs 111 ± 13), LH AUC (67 ± 21 vs 20 ± 9), FSH AUC (171 ± 59 vs 112 ± 29), respectively. Mean number of embryos transferred in both groups was similar. Number of pregnancies conceived (5 for flare and 10 for luteal protocol) was not significantly different. Although E₂ AUC in luteal protocol was higher than that in flare protocol, the difference was not statistically significant (28,339 ± 2,669 vs 26,905 ± 2,790). Differences in P and D₄ AUC between the two protocols were not statistically significant. Correlations with ovarian follicles and eggs retrieved were better for AMH than E₂. Conclusions: The luteal protocol exhibited a better ovarian response to stimulation as compared to the flare protocol. As compared to E₂, AMH had a better correlation with the number of follicles and eggs retrieved. / Medicine, Faculty of / Obstetrics and Gynaecology, Department of / Graduate

A síndrome de hiperestímulo ovariano (SHO) pode ocorrer de forma espontânea na gestação ou durante indução da ovulação para fertilização in vitro. Com o objetivo de identificar fatores clínicos e hormonais de risco para a SHO iatrogênica e analisar o papel das variantes alélicas do FSHR na sua etiologia, estudamos 29 pacientes com SHO iatrogênica moderada e grave. Idade < 33,5 anos, FSH basal < 5,2 UI/L e resposta de estradiol > 1757 pg/mL durante a estimulação ovariana atuaram como preditores independentes do risco de desenvolvimento da SHO iatrogênica, sendo a associação dos três fatores capaz de predizer a síndrome com acurácia de 78%. Não foram encontradas mutações nas 29 pacientes com SHO iatrogênica. Entretanto, o alelo Asn680 do polimorfismo Ser680Asn se associou às formas mais graves da SHO iatrogênica / Ovarian hyperstimulation syndrome (OHSS) can occur spontaneously during early pregnancy or as an iatrogenic complication in assisted reproductive medicine. The aim of this study was to identify clinical and hormonal risk factors for iatrogenic OHHS and to evaluate the role of allelic variants of the FSHR in the etiology of this syndrome. We studied 29 patients with moderate and severe iatrogenic OHHS. Age < 33.5 y, basal FSH < 5.2 U/L and estradiol response during ovarian stimulation > 1757 pg/mL were independent risk factors for iatrogenic OHSS and these three factors in association were able to predict the syndrome with accuracy of 78%. We did not find mutations in any patient studied. However, there was a predominance of the Asn680 allele of Ser680Asn polymorphism in patients with the most severe forms of the syndrome

A síndrome de hiperestímulo ovariano (SHO) pode ocorrer de forma espontânea na gestação ou durante indução da ovulação para fertilização in vitro. Com o objetivo de identificar fatores clínicos e hormonais de risco para a SHO iatrogênica e analisar o papel das variantes alélicas do FSHR na sua etiologia, estudamos 29 pacientes com SHO iatrogênica moderada e grave. Idade < 33,5 anos, FSH basal < 5,2 UI/L e resposta de estradiol > 1757 pg/mL durante a estimulação ovariana atuaram como preditores independentes do risco de desenvolvimento da SHO iatrogênica, sendo a associação dos três fatores capaz de predizer a síndrome com acurácia de 78%. Não foram encontradas mutações nas 29 pacientes com SHO iatrogênica. Entretanto, o alelo Asn680 do polimorfismo Ser680Asn se associou às formas mais graves da SHO iatrogênica / Ovarian hyperstimulation syndrome (OHSS) can occur spontaneously during early pregnancy or as an iatrogenic complication in assisted reproductive medicine. The aim of this study was to identify clinical and hormonal risk factors for iatrogenic OHHS and to evaluate the role of allelic variants of the FSHR in the etiology of this syndrome. We studied 29 patients with moderate and severe iatrogenic OHHS. Age < 33.5 y, basal FSH < 5.2 U/L and estradiol response during ovarian stimulation > 1757 pg/mL were independent risk factors for iatrogenic OHSS and these three factors in association were able to predict the syndrome with accuracy of 78%. We did not find mutations in any patient studied. However, there was a predominance of the Asn680 allele of Ser680Asn polymorphism in patients with the most severe forms of the syndrome

Objetivo: Avaliar o uso da bromocriptina na prevenção da síndrome do hiperestímulo ovariano (SHO) precoce moderada ou grave em mulheres de alto risco submetidas a fertilização in vitro. Pacientes e Métodos: Estudo duplo-cego, prospectivo e randomizado, foi realizado entre fevereiro de 2006 e novembro de 2007 no Centro de Reprodução Humana da Divisão de Ginecologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, na Huntington Centro de Medicina Reprodutiva e no Centro de Reprodução Humana do Hospital e Maternidade Santa Joana. Foram estudadas 28 mulheres entre 20 e 39 anos de alto risco para desenvolver a SHO (presença de 20 folículos ou mais ao ultrassom transvaginal no dia anterior à administração de gonadotrofina coriônica humana (hCG); níveis séricos de estradiol no dia da administração do hCG ou previamente a esta data iguais ou maiores que 3000 pg/ml e/ou aumento significativo ovariano bilateral). Foram divididas randomicamente, em dois grupos: A (n=17) e B (n=11), que receberam, respectivamente, um comprimido diário de ácido fólico (2,0 mg) e de bromocriptina (2,5 mg), por via oral, durante 14 dias, com início no dia da administração de hCG. As pacientes foram avaliadas no dia da administração do hCG (D1) e sete dias após (D2), quando foram realizados : ultrassom abdominal para verificar a presença de ascite; coleta de sangue para dosagens séricas de hemoglobina, hematócrito, leucócitos, plaquetas, uréia, creatinina, TGO, TGP e do fator de crescimento endotelial vascular (VEGF), e coleta de urina de 24 h para determinação de clearance de creatinina e concentração urinária de sódio. Resultados: Da série total (28 pacientes) que concluíram todo o estudo, 14 apresentaram ascite em D2, das quais 10 pertenciam ao grupo A (58,8%) e 4 (36,4%) ao grupo B (p=0,246). Destas 14 pacientes, 7 preencheram os critérios de gravidade, sendo que 6 pertenciam ao grupo A e, somente uma, ao grupo B. Observou-se aumento dos valores médios de VEGF no Grupo A (134,93 pg/ml) em D2, enquanto no Grupo B, houve diminuição (119,11pg/ml) (p=0,462).Conclusões: A bromocriptina não preveniu a SHO precoce moderada ou grave em pacientes de alto risco submetidas a fertilização in vitro, no entanto, houve diminuição da quantidade de líquido intraperitoneal e dos níveis séricos de VEGF. / Objective: To evaluate the effect of bromocriptine for the prevention of either early moderate or severe ovarian hyperstimulation syndrome (OHSS) in high risk women submitted to in vitro fertilization. Patients and Methods: A double-blind, prospective, randomized study was carried out between February 2006 and November 2007 at the Human Reproduction Center, Department of Gynecology, Teaching Hospital of the School of Medicine, University of São Paulo, at the Huntington Center of Reproductive Medicine and at the Human Reproduction Center of Santa Joana Hospital and Maternity Home. Twenty-eight women between 20 and 39 years of age, considered high risk for the development of OHSS (presence of 20 follicles at transvaginal ultrasonography on the day prior to human chorionic gonadotrophin [hCG] administration; serum estradiol levels 3000 pg/ml prior to or on the day of hCG administration and/or a significant bilateral increase in ovarian diameter), were included. The participants were randomly allocated to one of two groups. Women in group A (n=17) took a 2.0 mg tablet of folic acid and women in group B (n=11) took a 2.5 mg tablet of bromocriptine. Both treatments were taken orally daily for 14 days beginning on the day of hCG administration. Patients were evaluated on the day of hCG administration (D1) and seven days later (D2) at which time the following tests were performed: abdominal ultrasonography to detect the presence of ascites; blood sampling for the assessment of hemoglobin, hematocrit, leukocytes, platelets, urea, creatinine, SGOT, SGPT and vascular endothelial growth factor (VEGF). In addition, a 24-hour urine sample was collected to determine creatinine clearance and urinary sodium concentration. Results: All patients concluded the study. Fourteen had ascites at D2, 10 in group A (58.8%) and 4 (36.4%) in group B (p=0.246). Of these 14 patients, 7 fulfilled the criteria for severe OHSS, 6 in group A and 1 in group B. An increase was identified in mean VEGF values in group A (134.93 pg/ml) at D2, while a reduction was found in group B (119.11 pg/ml) (p=0.462). Conclusions: Bromocriptine did neither prevent early moderate nor severe OHSS in high risk patients submitted to in vitro fertilization; however, a reduction occurred in the intraperitoneal fluid volume and in serum VEGF levels.

Objetivo: Avaliar o uso da bromocriptina na prevenção da síndrome do hiperestímulo ovariano (SHO) precoce moderada ou grave em mulheres de alto risco submetidas a fertilização in vitro. Pacientes e Métodos: Estudo duplo-cego, prospectivo e randomizado, foi realizado entre fevereiro de 2006 e novembro de 2007 no Centro de Reprodução Humana da Divisão de Ginecologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, na Huntington Centro de Medicina Reprodutiva e no Centro de Reprodução Humana do Hospital e Maternidade Santa Joana. Foram estudadas 28 mulheres entre 20 e 39 anos de alto risco para desenvolver a SHO (presença de 20 folículos ou mais ao ultrassom transvaginal no dia anterior à administração de gonadotrofina coriônica humana (hCG); níveis séricos de estradiol no dia da administração do hCG ou previamente a esta data iguais ou maiores que 3000 pg/ml e/ou aumento significativo ovariano bilateral). Foram divididas randomicamente, em dois grupos: A (n=17) e B (n=11), que receberam, respectivamente, um comprimido diário de ácido fólico (2,0 mg) e de bromocriptina (2,5 mg), por via oral, durante 14 dias, com início no dia da administração de hCG. As pacientes foram avaliadas no dia da administração do hCG (D1) e sete dias após (D2), quando foram realizados : ultrassom abdominal para verificar a presença de ascite; coleta de sangue para dosagens séricas de hemoglobina, hematócrito, leucócitos, plaquetas, uréia, creatinina, TGO, TGP e do fator de crescimento endotelial vascular (VEGF), e coleta de urina de 24 h para determinação de clearance de creatinina e concentração urinária de sódio. Resultados: Da série total (28 pacientes) que concluíram todo o estudo, 14 apresentaram ascite em D2, das quais 10 pertenciam ao grupo A (58,8%) e 4 (36,4%) ao grupo B (p=0,246). Destas 14 pacientes, 7 preencheram os critérios de gravidade, sendo que 6 pertenciam ao grupo A e, somente uma, ao grupo B. Observou-se aumento dos valores médios de VEGF no Grupo A (134,93 pg/ml) em D2, enquanto no Grupo B, houve diminuição (119,11pg/ml) (p=0,462).Conclusões: A bromocriptina não preveniu a SHO precoce moderada ou grave em pacientes de alto risco submetidas a fertilização in vitro, no entanto, houve diminuição da quantidade de líquido intraperitoneal e dos níveis séricos de VEGF. / Objective: To evaluate the effect of bromocriptine for the prevention of either early moderate or severe ovarian hyperstimulation syndrome (OHSS) in high risk women submitted to in vitro fertilization. Patients and Methods: A double-blind, prospective, randomized study was carried out between February 2006 and November 2007 at the Human Reproduction Center, Department of Gynecology, Teaching Hospital of the School of Medicine, University of São Paulo, at the Huntington Center of Reproductive Medicine and at the Human Reproduction Center of Santa Joana Hospital and Maternity Home. Twenty-eight women between 20 and 39 years of age, considered high risk for the development of OHSS (presence of 20 follicles at transvaginal ultrasonography on the day prior to human chorionic gonadotrophin [hCG] administration; serum estradiol levels 3000 pg/ml prior to or on the day of hCG administration and/or a significant bilateral increase in ovarian diameter), were included. The participants were randomly allocated to one of two groups. Women in group A (n=17) took a 2.0 mg tablet of folic acid and women in group B (n=11) took a 2.5 mg tablet of bromocriptine. Both treatments were taken orally daily for 14 days beginning on the day of hCG administration. Patients were evaluated on the day of hCG administration (D1) and seven days later (D2) at which time the following tests were performed: abdominal ultrasonography to detect the presence of ascites; blood sampling for the assessment of hemoglobin, hematocrit, leukocytes, platelets, urea, creatinine, SGOT, SGPT and vascular endothelial growth factor (VEGF). In addition, a 24-hour urine sample was collected to determine creatinine clearance and urinary sodium concentration. Results: All patients concluded the study. Fourteen had ascites at D2, 10 in group A (58.8%) and 4 (36.4%) in group B (p=0.246). Of these 14 patients, 7 fulfilled the criteria for severe OHSS, 6 in group A and 1 in group B. An increase was identified in mean VEGF values in group A (134.93 pg/ml) at D2, while a reduction was found in group B (119.11 pg/ml) (p=0.462). Conclusions: Bromocriptine did neither prevent early moderate nor severe OHSS in high risk patients submitted to in vitro fertilization; however, a reduction occurred in the intraperitoneal fluid volume and in serum VEGF levels.

Das Ziel der Arbeit war es, mittels biochemischer und molekulargenetischer Untersuchungen die Rolle des partiellen 21-Hydroxylase-Mangels in der Pathogenese des Polyzystischen Ovar Syndroms (PCOS) und des Ovariellen Überstimulationssyndroms (OHSS) zu beleuchten sowie ein charakteristisches biochemisches Profil für Patientinnen mit erhöhtem Risiko zur Ausbildung eines OHSS aufzudecken. In die Studie wurden 62 Patientinnen eingeschlossen, 23 Kontrollpersonen und 39 PCOS-Patientinnen, von denen 17 Patientinnen anamnestisch mindestens eine Episode eines OHSS aufwiesen. Umfangreiche biochemische Analysen dienten zur Bestimmung der partiellen 21-Hydroxylase-Insuffizienz, zur Untersuchung des Ursprungs des Androgenüberschusses (ACTH und LHRH-Test) und zur Charakterisierung des metabolischen Profils (Leptin, Insulin, SHBG, IGF-1). Zur Darstellung des Gentotyps führten wir die lückenlose Untersuchung des CYP21A2-Gens auf Mutationen und Polymorphismen durch. Die androgenen Steroide wiesen ein bei den PCOS-Patientinnen im Vergleich zu den Kontrollpatientinnen erhöhtes Niveau auf, ohne dass sich ein klare Unterscheidung zwischen adrenalem und ovariellem Ursprung abzeichnete. Bei den OHSS-Patientinnen dominierten die ovariellen Androgene. Die Leptinwerte waren in der PCOS-Gruppe erhöht, besonders bei den Patientinnen mit OHSS. Die Frequenz heterozygoter Punktmutationen lag in unserer PCOS-Gruppe mit 23% deutlich höher als in der Kontrollgruppe mit 8%. Es ergab sich kein signifikanter Unterschied zwischen PCOS-Patientinnen mit und ohne OHSS. Die Allelfrequenz der detektierten Polymorphismen unterschied sich nicht zwischen PCOS-Patientinnen und Kontrollen. Von insgesamt 17 Patientinnen mit biochemischen Auffälligkeiten waren 8 Trägerinnen einer heterozygoten Mutation. Im Gegensatz dazu wiesen nur 8 der 11 Patientinnen mit Punktmutation biochemische Abweichungen auf. Es ergab sich also nicht für jeden Fall eine eindeutige Genotyp-Phänotyp-Korrelation. / This study was designed to evaluate the possible role of partial 21-Hydroxylase Deficiency in the pathogenesis of the Polycystic Ovary Syndrome (PCOS) and the Ovarian Hyperstimulation Syndrome (OHSS) by means of biochemical and molecular genetic investigations, as well as to identify the biochemical profile typical of patients with an elevated risk of developing an OHSS. 62 female patients were included in the study, 23 controls and 39 PCOS patients. 17 of these had at least one anamnestic episode of OHSS. Extensive biochemical investigations were used to determine partial 21-OHase Deficiency as well as the source of the androgen excess (ACTH and LHRH tests) and to describe the metabolic profile (leptin, insulin, SHBG and IGF-1). For genotypic characterization, we screened the CYP21A2 gene for any mutation or polymorphism. Androgens were elevated in the PCOS group without a clear differentiation into adrenal or ovarian origin. Amongst patients with OHSS, the ovarian androgens were dominant. Higher leptin levels were measured in the PCOS group, especially in patients with OHSS. The frequency of heterozygous point mutations was 23% in our PCOS group, compared to 8% amongst control patients. There was no relevant difference between PCOS patients with or without an OHSS. The frequency of polymorphisms did not differ between the groups. We found relevant heterozygous point mutations in 8 of the 17 patients with biochemical deviations. In contrast to this only 8 of the 11 patients with point mutations showed biochemical derangements indicating no clear Genotype-Phenotyp-correlation.

Abstract The main goal of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment is a healthy mother and a healthy child. The most important complication following IVF/ICSI arises from the increased risk of multiple pregnancies. An elective single embryo transfer (eSET) with the freezing of spare embryos and subsequent treatment with frozen embryo transfer (FET) is the only way to avoid this complication. For this reason, the number of children born after FET is steadily rising. The aim of this study was to provide more detailed evidence on the safety of FET, particularly focusing on serum hormone profiles during the first trimester weeks of singleton pregnancies after IVF/ICSI fresh embryo transfer (ET), after FET during a natural menstrual cycle, and after spontaneous conception. Another part of this study compared the perinatal outcomes, congenital anomalies (CAs), and morbidity of singletons born after FET and IVF/ICSI fresh ET. The reference group was those born after spontaneously conceived (SC) pregnancies. In the clinical prospective study, the maternal serum estradiol and progesterone levels in pregnancies after fresh ET (n=39) were higher during early pregnancy weeks than in FET (n=30) and SC pregnancies (n=41), while the hormonal profiles after FET did not differ from SC pregnancies. In the large register study, FET children (n=1830) were found to have a reduced risk for adverse perinatal outcomes, such as preterm birth, a low birthweight, and being small for their gestational age compared with children born after fresh ET (n=2942). However, FET children have an increased risk for being large for their gestational age. The major CAs and morbidity until three years of age did not differ between groups. When compared with SC children (n =31 243), the perinatal outcome was worse and the rates of CAs and morbidity were higher in FET children. The FET cycle seemed to provide a better physiological environment for early fetal development than fresh ET. Further, FET protects against some of the adverse perinatal outcomes of children when compared with fresh ET, but not when it comes to the major CAs and early somatic health. This study provides further evidence of the safety of FET in comparison with fresh ET. This information should further encourage clinicians to implement eSET combined with cryopreservation in their IVF/ICSI program. / Tiivistelmä Koeputkihedelmöityshoidon (in vitro fertilization, IVF ja intracytoplasmic sperm injection, ICSI) tavoitteena on terve äiti ja terve lapsi. Monisikiöraskaus on hoidon komplikaatio, koska siihen liittyy selkeästi kohonnut riski äidille ja lapselle. Yhden alkion siirto, jäljelle jääneiden alkioiden pakastus ja myöhemmin tehtävä pakastetun alkion siirto (PAS) ovat lisänneet IVF/ICSI-hoitojen turvallisuutta ja tehokkuutta. Täten PAS:sta syntyneiden lasten määrä kasvaa. Tutkimuksen tavoitteena on lisätä PAS-hoitojen turvallisuutta tarkastelemalla veren steroidihormonien muutoksia alkuraskaudessa naisilta, jotka olivat tulleet raskaiksi IVF/ICSI-tuorealkion siirroista, luonnollisen kuukautiskierron aikana tehdystä PAS:sta ja luonnollisesti. Lisäksi tutkimuksessa verrattiin PAS- ja IVF/ICSI-tuorealkion siirrosta alkunsa saaneiden lasten terveyttä kolmeen ikävuoteen asti. Viiteryhmän muodostivat luonnollisesti alkunsa saaneet lapset. Kliinisessä prospektiivisessa tutkimuksessa havaittiin naisilla, joilla oli tuorealkion siirrosta alkanut raskaus (n=39), merkittävästi koholla olevat seerumin estradioli- ja progesteronipitoisuudet 7-8 raskausviikolle asti verrattuna naisiin, joilla raskaudet olivat alkaneet PAS:sta (n=30) tai luonnollisesti (n=41). Vastaavasti PAS-raskauksissa hormonipitoisuudet eivät eronneet merkittävästi luonnolliseen raskauteen verrattuna. Laajassa rekisteritutkimuksessa havaittiin PAS-lapsilla (n=1830) olevan pienempi riski ennenaikaisuuteen ja pienipainoisuuteen kuin tuorealkiolapsilla (n=2942). Kuitenkin PAS-lapsilla oli lisääntynyt riski syntyä isokokoisina raskausviikkoihin nähden. Synnynnäisten epämuodostumien ja eri sairauksien esiintyvyyksissä ei ollut eroja. Luonnollisesti alkunsa saaneisiin lapsiin (n= 31 243) verrattaessa, PAS-lapsilla oli vastasyntyneisyyskaudelta lähtien enemmän terveyteen liittyviä ongelmia. Tutkimus osoitti PAS-raskaudessa sikiön kehittyvän alkuviikkoina luonnollisemmassa ympäristössä kuin tuorealkion siirtoraskaudessa. Vaikka suurin osa PAS- ja tuorealkiolapsista oli terveitä, tuorealkiolapsilla oli vastasyntyneisyyskaudella enemmän ongelmia kuin PAS-lapsilla. Muita terveyseroja lasten välillä ei todettu. Tutkimus antaa lisänäyttöä PAS hoidon turvallisuudesta. Alkion pakastamisella voidaan välttää koeputkihedelmöityshoidon riskejä pyrkimällä mahdollisimman usein yhden alkion siirtoon.