Search

Objective: To evaluate the impact of the regressing corpus luteum on the hormone secretion during hCG stimulation. The hCG stimulation test in the early follicular phase has been used to assess the capacity of the ovarian theca cells to secrete steroids. Design: A prospective observational study. Setting: University hospital. Patient(s): The study group consisted of 11 women with confirmed ovulation in the past cycle (corpus luteum positive [CL+]) and the control group of 11 women using oral contraceptive pills (OC; no CL). Intervention(s): An hCG test (5,000 IU IM) was performed 2 to 4 days after menstrual bleeding, and the ovarian response was measured at 0, 48, and 96 hours after injection. Main Outcome Measure(s): Changes in serum concentrations of P, 17-hydroxyprogesterone (17-OHP), androstenedione (A), T, E(2), and vascular endothelial growth factor (VEGF), and in ovarian vasculature and volume (three-dimensional power Doppler ultrasonography) were measured. Result(s): Secretion of P and 17-OHP increased after hCG injection in the CL group, whereas no change was observed in women on OCs (P < or = .001). Concomitant increases were observed in volume and vasculature of the ovary with a CL (P<.05), but not in the contralateral ovary or in women on OCs. The changes in volume and vasculature correlated with levels of P and 17-OHP (P<.05). Conclusion(s): The regressing corpus luteum from the past menstrual cycle reactivates and secretes steroids in response to hCG stimulation performed during the early follicular phase, which should be taken into account when comparing hormone profiles of ovulatory and anovulatory women. [ABSTRACT FROM AUTHOR]

Objective: The growth of the follicles induced by gonadotropins during IVF treatment is accompanied by physiologic angiogenesis, which is essential for the maturation of the oocytes. We describe the IVF-induced changes in the vascularization and compare normal with polycystic ovaries (PCOs). Design: Prospective study. Setting: Assisted reproductive unit at a university hospital. Patient(s): Sixty women who underwent IVF cycles. Intervention(s): The ovarian vascularization was measured after pituitary down-regulation, FSH stimulation, and hCG-injection using three-dimensional power Doppler ultrasonography. Main Outcome Measure(s): The total ovarian vascularization was divided by the number of follicles. Result(s): After pituitary suppression, the ovarian vascularization/follicle was lower in polycystic ovary (PCO) patients. During ovarian stimulation, follicles in PCOs required a lesser amount of FSH to acquire the same level of vascularization than the follicles in normal ovaries. In addition, hCG induced an increase in the follicular vascularization in both normal and PCOs. The follicle count correlated with the total vascularized volume in the ovaries throughout the IVF cycle. Conclusion(s): Follicles in PCOs seem to be less vascularized than the follicles in normal ovaries after GnRH treatment but not after gonadotropin stimulation. It is possible that restricted blood supply to the follicles in PCO might be associated with the follicular arrest that is observed. We could confirm that follicles in PCO are more sensitive to gonadotropin stimulation than follicles in normal ovaries. [ABSTRACT FROM AUTHOR]

: ObjectiveTo evaluate the changes taking place in the ovaries during pituitary down-regulation.: DesignProspective observational study of women undergoing IVF treatment.: SettingA tertiary referral center for assisted reproduction.: Patient(s)Forty women who received the long buserelin acetate treatment protocol.: Intervention(s)Transvaginal three-dimensional power Doppler ultrasound examinations before and after pituitary down-regulation.: Main outcome measure(s)Ovarian volume, number of follicles, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and mean gray value (MG).: Result(s)Before the pituitary down-regulation, the dominant ovary was larger in volume and had a lower MG than the nondominant ovary. After the down-regulation, there was a significant decrease in the volume and number of follicles and an increase in MG. After pituitary down-regulation, the dominant and nondominant ovaries did not differ from each other in any of the parameters. Polycystic ovaries were larger than normal ones before and after the down-regulation, without any differences in MG, VI, FI, or VFI. Right and left ovaries did not differ from each other after the down-regulation.: Conclusion(s)The differences observed between dominant and nondominant ovaries seem to disappear after pituitary down-regulation. In addition, polycystic ovaries were always larger than the normal ones, but no differences could be detected in the stromal brightness or vascularity either before or after the administration of GnRH agonist therapy. [Copyright &y& Elsevier]

STUDY QUESTION Are there differences in estrogen and progesterone secretion in singleton pregnancies, up to Week 11, between spontaneous pregnancies, after controlled ovarian hyperstimulation and fresh embryo transfer (COH + ET) and after frozen embryo transfer in a spontaneous cycle (FET)? SUMMARY ANSWER Serum progesterone and estradiol (E2) concentrations after COH + ET were higher in early pregnancy, lasting up to Week 7–8, than FET and spontaneous pregnancies, while hormone levels after FET did not differ from spontaneous pregnancies. WHAT IS ALREADY KNOWN The risk of adverse perinatal outcomes after COH + ET seems to be increased when compared with spontaneous pregnancies. One of the reasons suggested for this is related to ovarian hyperstimulation. STUDY DESIGN, SIZE, DURATION This was a prospective cohort study consisting of three different groups of pregnant women which were followed-up weekly until Week 11 of their pregnancies. The spontaneous pregnancy group consisted of 41 women, the COH + ET group consisted of 39 and the FET group consisted of 30 women. PARTICIPANTS/MATERIALS, SETTING, METHODS Women in the control group with spontaneous conception were recruited from local prenatal clinics. Women in the COH + ET and FET groups were recruited from the Reproductive Unit of Oulu University Hospital. At each visit, a three-dimensional ultrasonography was performed to examine the ovarian volumes and vascularization. A blood sample was drawn to analyse progesterone and E2 levels. The pregnancy outcome was included in the analysis. MAIN RESULTS AND THE ROLE OF CHANCE At pregnancy Week 5, the serum progesterone levels were higher after the COH + ET (median 312, inter-quartile range 183–480 nmol/l), when compared with the spontaneous (63, 52–80 nmol/l; P < 0.001) and FET (74, 48–96 nmol/l; P < 0.001) pregnancies. At Week 11, the P (189, 124–260 nmol/l) was still higher in the COH + ET group (FET 101, 78–120 nmol/l, P < 0.001; spontaneous 115, 80–139 nmol/l, P < 0.01) than the other two groups. The E2 levels at Week 5 were also significantly higher after COH + ET (4.1, 2.2–6.6 nmol/l) than in the spontaneous pregnancies (1.1, 0.7–1.6 nmol/l, P < 0.001) or after FET (0.7, 0.6–0.9 nmol/l, P < 0.001). The volume of the ovaries and the intraovarian vasculature in the COH + ET group were significantly higher when compared with the other two groups (P < 0.001). The birthweight was negatively correlated with the serum P (R −0.340, P < 0.01) and E2 (R= −0.275, P < 0.05) in pregnancy Weeks 5–8. In the multivariate analysis evaluating the factors affecting birthweight of the newborn, the significant factors were the length of gestation, maternal height and progesterone or E2 secretion during Weeks 5–8. LIMITATIONS, REASONS FOR CAUTION Because of the low number of patients in this study, larger cohort studies are required to confirm the findings. WIDER IMPLICATIONS OF THE FINDINGS The findings here indicate that COH-induced increased luteal activity should be evaluated by measuring steroid levels or the ovarian size or vascularity, rather than number of oocytes retrieved. If unphysiologically high steroid activity during pregnancy after COH contributes to the risk of adverse perinatal outcomes after fresh embryo transfer, milder stimulation protocols or even freezing of all of the embryos should be considered. STUDY FUNDING/COMPETING INTERESTS This study was supported by a research grant from the Academy of Finland. The authors declare no conflicts of interest. [ABSTRACT FROM PUBLISHER]

Background: In natural cycles, women conceive when intercourse takes place during a six-day period ending on the day of ovulation. The current practice in intrauterine insemination (IUI) cycles is to perform the IUI 24-36 hours after the hCG administration, when the ovulation is already imminent. In this study hCG was administered after the IUI, which more closely resembles the fertilisation process in natural cycles. Methods: All the IUIs performed since the beginning of 2007 were analysed retrospectively. Our standard protocol has been to perform the IUI 24-32 hours after hCG administration. From the end of 2008, we started to inject hCG after the IUI at random. The main outcome measure was the result of a urinary pregnancy test. Generalized Estimating Equations (GEE) was used to identify independent factors affecting the cycle outcome. Results: The analysis included 228 cycles with hCG administered before and 104 cycles hCG administered after the IUI. The pregnancy rates were 10.9% and 19.6% (P = 0.040), respectively. Independent factors (OR, 95% CI) affecting the cycle outcome were sperm count (2.65, 1.20-5.81), number of follicles > 16 mm at IUI (2.01, 1.07-3.81) and the time of hCG administration (2.21, 1.16-4.19). Conclusion: Improved pregnancy rate was observed with administration of hCG after IUI. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Our aim was to evaluate the predictive value of gestational diabetes mellitus (GDM), diabetes-associated autoantibodies, and other factors for development of clinical diabetes later in life. RESEARCH DESIGN AND METHODS -- In this case-control study the presence of autoantibodies was studied in 435 women with GDM and in healthy matched control subjects. The need for exogenous insulin during GDM was recorded. In the GDM group, the mean follow-up period was 5.7 years and in the control group 6.1 years. RESULTS -- Among the subjects with GDM, 20 (4.6%) developed type 1 diabetes and 23 (5.3%) developed type 2 diabetes, whereas none of the control subjects became diabetic. Two-thirds of those who developed type 1 diabetes tested positive initially for islet cell antibodies (ICAs), whereas 56% of them had autoantibodies to GAD (GADAs) and 38% to the protein tyrosine phosphatase-related IA-2 molecule. Only 2 of the 23 women who presented later with type 2 diabetes tested positive for autoantibodies. According to multivariate analysis, initial age ≤30 years, the need for insulin treatment for GDM, and antibody positivity for ICAs and GADAs were associated with increased risk for clinical type 1 diabetes. CONCLUSIONS -- Pregnancy seems to identify women who are at risk of developing diabetes later in life. About 10% of Finnish women with GDM will develop diabetes over the next 6 years; nearly half of them develop type 1 diabetes and the other half type 2 diabetes. Age ≤30 years, the need for insulin treatment during pregnancy, and positivity for ICAs and GADAs confer a high risk of subsequent progression to type 1 diabetes in women affected by GDM. [ABSTRACT FROM AUTHOR]

Objective: To study the predictive value of initial low response (LR) in IVF/intracytoplasmic sperm injection (ICSI). Design: Retrospective analysis. Setting: Two Finnish fertility centers. Patient(s): A total of 3,846 IVF/ICSI cycles performed from 1994 to 2002. Intervention(s): Consecutive cycles in the same subject were identified. The study groups consisted of subjects who had three treatment cycles and at least one LR cycle (n = 80). Main Outcome Measure(s): Pregnancy rate (PR), total gonadotropin dose, and embryo quality. Result(s): Only 2.5% (2/80) of subjects had a LR in all three consecutive cycles. In 43 women an initial LR was followed by ?1 normal response (NR) cycle, and in 35 women an initial NR was followed by ?1 LR cycle. The PR/cycle was similarly low in women with an initial LR and an initial NR (10.1% vs. 16.2%). An increase in gonadotropin dose resulted in a higher number of oocytes in women with an initial LR (from 2.1 ± 0.9 to 6.7 ± 2.7) but the PR/cycle remained low, compared to the overall mean PR (27.2%). In cycles in which top quality embryos were transferred, subjects with an initial LR had a lower PR than women with an initial NR (17.8% vs. 41.2%). Conclusion(s): An initial LR is a predictor of poor outcome in subsequent cycles, even if ovarian response is improved by increasing the gonadotropin dose or a top quality embryo is replaced. [Copyright &y& Elsevier]

: ObjectiveTo evaluate whether power Doppler predicts ovarian response to gonadotrophin stimulation during in vitro fertilization (IVF).: MethodsForty-five women were divided into low-reserve (n = 12) and normal-reserve (n = 33) ovarian groups, according to antral follicle count. Transvaginal three-dimensional power Doppler ultrasonographic examinations were performed after pituitary downregulation and after gonadotrophin stimulation. The antral follicle count, ovarian volume, vascularization index, flow index, vascularization flow index, and mean gray value were measured and related to the number of oocytes retrieved and the pregnancy rate.: ResultsThe number of oocytes retrieved correlated with the antral follicle count (R = .458, P = .004) and ovarian volume (R = .388, P < .016) but not with vascularization index, flow index, vascularization flow index, or mean gray value after pituitary suppression. There was an increase in vascularization index (P < .017), flow index (P < .001), and vascularization flow index (P < .007) during gonadotrophin stimulation in the normal-ovary group but not in the low-ovarian-reserve group.: ConclusionAccording to our results, quantification of power Doppler signal in the ovaries after pituitary suppression does not provide any additional information to predict the subsequent response to gonadotrophin stimulation during IVF. The increase in ovarian power Doppler signal during gonadotrophin stimulation is related to the antral follicle count observed after pituitary suppression. [Copyright &y& Elsevier]

Background: We wished to investigate the correlation between a new Down screening marker ADAM12 (a disintegrin and metalloproteinase-12) and pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) during the first trimester of pregnancy. Methods: ADAM12, PAPP-A and fbeta-hCG were measured in 225 serum samples of randomly chosen pregnancies with completely normal outcome. The samples were taken between pregnancy weeks 9+0 and 12+6. Results: The ADAM12 levels tended to increase with advanced gestational age and the highest levels were detected at pregnancy week 12. The ADAM12 levels correlated with PAPP-A levels. After weight correction and logarithmic transformation the multiples of median (MoM) of ADAM12 still correlated with the MoMs of PAPP-A and also with the MoMs of fbeta-hCG. Smokers had lower ADAM12 levels than non-smokers. Conclusion: The secretion of ADAM12 seems to resemble the secretion of PAPP-A in the end of the first trimester. Accordingly ADAM12 appears not to be a separate marker independent of PAPP-A. It remains to be assessed whether adding ADAM12 in Down screening risk calculation will reduce the false positive rate during the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary leiomyomatosis and renal cell cancer (HLRCC) constitute a tumor susceptibility syndrome caused by germline mutations in the fumarate hydratase (FH) gene. The most common features are leiomyomas of the uterus and the skin. The syndrome includes a predisposition to early‐onset, aggressive renal cell cancer. It is important to identify women with HLRCC among other uterine leiomyoma patients in order to direct them to genetic counseling and to identify other affected family members. Material and methods: We conducted a nationwide historical study to identify typical clinical characteristics, uterine leiomyoma morphology, and immunohistochemistry for diagnosing HLRCC. The study included 20 women with a known FH germline mutation and 77 women with sporadic uterine leiomyomas. The patient records of all women were reviewed to obtain clinical details regarding their leiomyomas. Uterine leiomyoma tissue specimens from 43 HLRCC‐related leiomyomas and 42 sporadic leiomyomas were collected and prepared for histology analysis. A morphologic description was performed on hematoxylin & eosin‐stained tissue slides, and immunohistochemical analysis was carried out for CD34, Bcl‐2, and p53 stainings. Results: The women with HLRCC were diagnosed with uterine leiomyomas at a young age compared with the sporadic leiomyoma group (mean 33.8 years vs. 45.4 years, P < 0.0001), and their leiomyomas occurred as multiples compared with the sporadic leiomyoma group (more than four tumors 88.9% vs. 30.8%, P < 0.0001). Congruently, these women underwent surgical treatment at younger age compared with the sporadic leiomyoma group (mean 37.3 years vs. 48.3 years, P < 0.0001). HLRCC leiomyomas had denser microvasculature highlighted by CD34 immunostaining when compared with the sporadic leiomyoma group (112.6 mean count/high‐power field, SD 20.8 vs. 37.4 mean count/high‐power field, SD 21.0 P < 0.0001) and stronger anti‐apoptotic protein Bcl‐2 immunostaining when compared with the sporadic leiomyoma group (weak 4.7%, moderate 44.2%, strong 51.2% vs. 26.2%, 52.4%, 21.4%, respectively, P = 0.003). No differences were observed in p53 staining. Conclusions: Women with HLRCC may be identified through the distinct clinical characteristics: symptomatic and numerous leioymyomas at young age, and morphologic features of FH‐mutant leiomyomas, aided by Bcl‐2 and CD34 immunohistochemistry. Further, distinguishing individuals with a germline FH mutation enables proper genetic counseling and regular renal monitoring. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to evaluate the predictive value of gestational diabetes mellitus (GDM), diabetes-associated autoantibodies, and other factors for development of clinical diabetes later in life.Research Design and Methods: In this case-control study the presence of autoantibodies was studied in 435 women with GDM and in healthy matched control subjects. The need for exogenous insulin during GDM was recorded. In the GDM group, the mean follow-up period was 5.7 years and in the control group 6.1 years.Results: Among the subjects with GDM, 20 (4.6%) developed type 1 diabetes and 23 (5.3%) developed type 2 diabetes, whereas none of the control subjects became diabetic. Two-thirds of those who developed type 1 diabetes tested positive initially for islet cell antibodies (ICAs), whereas 56% of them had autoantibodies to GAD (GADAs) and 38% to the protein tyrosine phosphatase-related IA-2 molecule. Only 2 of the 23 women who presented later with type 2 diabetes tested positive for autoantibodies. According to multivariate analysis, initial age < or =30 years, the need for insulin treatment for GDM, and antibody positivity for ICAs and GADAs were associated with increased risk for clinical type 1 diabetes.Conclusions: Pregnancy seems to identify women who are at risk of developing diabetes later in life. About 10% of Finnish women with GDM will develop diabetes over the next 6 years; nearly half of them develop type 1 diabetes and the other half type 2 diabetes. Age < or =30 years, the need for insulin treatment during pregnancy, and positivity for ICAs and GADAs confer a high risk of subsequent progression to type 1 diabetes in women affected by GDM. [ABSTRACT FROM AUTHOR]