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.

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

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.