Ilkka Y. Järvelä

Quantification of ovarian power Doppler signal with three-dimensional ultrasonography to predict response during in vitro fertilization

OBJECTIVE To evaluate whether power Doppler predicts ovarian response to gonadotrophin stimulation during in vitro fertilization (IVF). METHODS Forty-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. RESULTS The 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. CONCLUSION According 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.

Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure

BackgroundTrophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs).MethodsThis study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89).ResultsMMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies.ConclusionsHuman placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.

Characterization of Normal and Polycystic Ovaries Using Three-Dimensional Power Doppler Ultrasonography

AbstractPurpose: To evaluate the characteristics of polycystic compared to normal ovaries using three-dimensional (3-D) power Doppler ultrasonography. Methods: We recruited 42 volunteers, all of whom were commencing IVF treatment. Each patient was examined in the cycle preceeding the start of drug therapy during the late follicular phase. If eight or more subcapsular follicles of 2–8 mm in diameter in one two-dimensional (2-D) plane were detected in either of the ovaries, the patient was categorized as having polycystic ovaries (PCO); otherwise the ovaries were considered normal. The parameters examined were volume of the ovary, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and mean greyness (MG). In addition, the ovary was arbitrarily divided into cortex and stroma, and thereafter volume, VI, FI, VFI, and MG were calculated for these two regions. Results: Twenty-eight women had normal ovaries and 14 had PCO. The comparison between normal and PCO showed that as a group the PCO were larger, without any differences in VI, FI, VFI, or MG. In patients with PCO, the right ovary was larger than the left one. In patients with normal ovaries, FI was higher on the left side. Division into cortex and stroma revealed that there were no differences in cortical or stromal VI, FI, VFI, or MG between normal and PCO on either side. Conclusions: The ovaries defined as polycystic were larger than normal ovaries, but there was no difference in the echogenicity of the stroma between polycystic and normal ovaries. We were also unable to demonstrate that the polycystic ovarian stroma was more vascularized than the stroma in the normal ovaries.

Evaluation of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase gene mutations in patients with severe pregnancy complications in northern Finland.

Background: Thrombosis in placenta may lead to severe pregnancy complications. Most important inherited thrombophilias are factor V Leiden mutation, prothrombin mutation, and methylenetetrahydrofolate reductase mutation. The aim of our research was to evaluate the prevalence of inherited thrombophilias in severe pregnancy complications and in normal pregnancies. Material and Methods: The study subjects with severe preeclampsia, intrauterine growth restriction, placental abruption or fetal death were collected during the period 1999–2004 from Oulu University Hospital. We also collected during the same period voluntary parturients with normal pregnancy outcome as the control group. FVL, FII, and MTHFR gene mutations of the patients and controls were analyzed. Results: We found a significant difference in the prevalence of FVL mutation between the groups. There were 9.5% FVL mutations in the study group compared to 1.8% in the control group; the observed difference between prevalences was 7.7% (95% CI 2.0–13.4). No statistical difference was found in the FII or MTHFR mutations between the groups. All FV and FII mutations were heterozygous and all the MTHFR mutations homozygous. Conclusion: Women with thrombophilia have a risk for severe pregnancy complications. Randomized controlled trials are needed to assess the influence of low-molecular-weight heparin in pregnant women with thrombophilia.

Assessment of endometrial and ovarian characteristics using three dimensional power Doppler ultrasound to predict response in frozen embryo transfer cycles

ObjectiveTo evaluate whether endometrial or ovarian parameters as measured using 3D power Doppler ultrasound would predict the outcome in frozen embryo transfer (FET) cycles.MethodsThirty women with no known gynecological pathology undergoing FET were recruited. The FET was carried out in the natural menstrual cycle 3-4 days after the first positive LH test result. Blood samples for hormonal analysis were collected, and three-dimensional (3D) ultrasonographic examination was performed on the day of the FET and repeated with analysis of the total hCG one week later.ResultsThe demographic, clinical, and embryological characteristics were similar between the pregnant (15/30) and nonpregnant groups (15/30). There were no differences between the groups in endometrial/subendometrial thickness, volume, or vascularization index (VI). The endometrial triple-line pattern was more often present in the pregnant group on the day of the FET (93.3% vs. 40.0%, 95% CI 25.5-81.2%). No differences in the ovaries were observed on the day of the FET. At the second visit, the triple-line pattern was still more often present in those patients who had conceived (91.7% vs. 42.9%, 95% CI 18.5-79.1%), and their corpus luteum was more active as judged by the rise in 17-hydroxyprogesterone and estradiol levels. No differences were observed in the dominant ovarian vasculature.ConclusionsAccording to our results, measurement of power Doppler indices using 3D ultrasound on the day of the FET does not provide any additional information concerning the outcome of the cycle. The existence of the triple-line pattern on the day of the FET seems to be a prognostic sign of a prosperous outcome after FET. The dominant ovary in the pregnant group seems to be already activated one week after the FET.

The secretion of PAPP-A, ADAM12, and PP13 correlates with the size of the placenta for the first month of pregnancy

OBJECTIVES Pregnancy Associated Protein A (PAPP-A), A Disintegrin and Metalloproteinase 12 (ADAM12) and Placental Protein 13 (PP13) are secreted from the placental trophoblastic tissue and are involved in normal implantation and placental development. The aim of the study was to assess the connection between the secretion of these proteins and the growth of the gestational sac and the placenta. STUDY DESIGN In an observational longitudinal study at Oulu University Hospital, women with naturally conceived pregnancies were followed-up weekly to pregnancy week 11. MAIN OUTCOME MEASURES PAPP-A, ADAM12 and PP13 serum concentrations and their correlation with the volumes of the gestational sac and the placenta were assessed using three-dimensional ultrasonography. RESULTS The study group consisted of 41 women. The PAPP-A, ADAM12 and PP13 serum concentrations increased continuously from pregnancy week 4 to week 11 and correlated closely with each other. The serum concentrations of PAPP-A, ADAM12 and PP13 also correlated with the volumes of the gestational sac and the placenta up to pregnancy week 8. CONCLUSIONS The secretion of PAPP-A, ADAM12 and PP13 is closely related to the size of the placenta in the beginning of pregnancy. After 8 weeks of pregnancy, which is the time for luteoplacental shift, the correlation disappears, possibly reflecting the morphologic transformation in the placenta.

In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies

The maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) were reduced in hormonally stimulated pregnancies in the in vitro fertilization and intracytoplasmic sperm injection groups (N=176; PAPP-A: 0.82) and in the entire assisted reproduction group (N=282; PAPP-A: 0.83) as compared with controls (N=24,783; PAPP-A: 0.94). However, the false-positive rate of first-trimester combined screenings was not statistically significantly increased in assisted reproduction pregnancies after adjustment for maternal age.

Improved pregnancy rate with administration of hCG after intrauterine insemination: a pilot study

BackgroundIn 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.MethodsAll 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.ResultsThe 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).ConclusionImproved pregnancy rate was observed with administration of hCG after IUI.

Effect of rising hCG levels on the human corpus luteum during early pregnancy.

BACKGROUND During early pregnancy, the most important task of the corpus luteum (CL) is to produce sufficient progesterone until the luteoplacental shift occurs. Progesterone production is closely related to the extensive vasculature surrounding and supplying the CL. The synthesis of both progesterone and factors controlling the vasculature in the CL is regulated by hCG, which is released initially at rising levels from the placenta. The primary aim of this research was to evaluate changes in the CL vasculature during early pregnancy. METHODS Twenty naturally conceived pregnancies were examined weekly from weeks 5 to 11. At each visit, blood samples were obtained to determine the concentrations of hCG, progesterone and 17-OH progesterone (17-OHP). The vasculature in the ovaries was assessed using three-dimensional power Doppler ultrasonography. RESULTS The vascular supply in the ovary containing the CL was greatest at week 5, and thereafter, declined continuously until week 11. The decrease in the vasculature correlated with the decrease in 17-OHP. Mean hCG levels reached a maximum at week 8, progesterone levels reached the nadir at week 7 and increased after that. CONCLUSIONS Vasculature in the CL appears to be created already by the fifth week of pregnancy and it does not enlarge despite rising hCG levels. The activity of the CL during pregnancy may be measured non-invasively by assessing its vasculature with three-dimensional ultrasonography.

Do symptomatic endometriosis and uterine fibroids appear together

OBJECTIVES: Endometriosis and uterine fibroids are common gynecological disorders in fertile women. It has been suggested that these two disorders may be associated with each other. In this study, we tested whether this connection exists. In addition, we wanted to evaluate whether they both affect fertility independently of each other. MATERIALS AND METHODS: The prevalence of endometriosis and uterine fibroids was investigated in three groups of patients: Symptomatic patients requiring surgery either for endometriosis (n=182), or for uterine fibroids (n=240) and asymptomatic patients undergoing laparoscopic sterilization (n=183). The prevalences were examined in three age groups: 35–39 yrs, 40–44 yrs and ≥ 45 yrs. The significance of both diagnoses on fertility was assessed using logistic regression analysis. RESULTS: Uterine fibroids were detected in 25.8% (47/182) of patients with endometriosis. Endometriosis was detected in 19.6% (47/240) of patients with uterine fibroids. 5.5% (10/183) women undergoing sterilization had endometriosis and 19.3% (17/183) had uterine fibroids. Both uterine fibroids and endometriosis were, independently of each other, related to subfertility (OR, 95% CI: 3.8, 2.3–6.5; 6.8, 4.0–11.6, respectively). CONCLUSIONS: The results suggest that symptomatic endometriosis appears together with symptomatic uterine fibroids. Both diseases seem to decrease female fertility independently of each other.