Aila Tiitinen

Urinary tract injuries after hysterectomy

Objective To evaluate the nationwide incidence and characteristics of urinary tract injuries after laparoscopic hysterectomy, total abdominal hysterectomy, supracervical abdominal hysterectomy, and vaginal hysterectomy. Methods We analyzed retrospectively 142 urinary tract injuries after hysterectomy, reported to the National Patient Insurance Association in Finland from 1990 through 1995. The Finnish Hospital Discharge Register collects data on procedures from all hospitals, and 62,379 hysterectomies were carried out during the study period. Results The total incidence of ureteral injury after all hysterectomies was 1.0 of 1000 procedures: 13.9 of 1000 after laparoscopic, 0.4 of 1000 after total abdominal, 0.3 of 1000 after supracervical abdominal, and 0.2 of 1000 after vaginal hysterectomy. Difficulties during an operation with a ureteral injury were encountered in 51%, 76%, 100%, and 100%; the failure rates of primary repair of a ureteral injury were 5%, 12%, 0%, and 0%; and the convalescence times after a ureteral injury were 86 days, 94 days, 71 days, and 47 days after laparoscopic, abdominal, supracervical abdominal, and vaginal hysterectomies, respectively. The incidence of bladder injury was 1.3 of 1000 procedures. Sixty-five percent of reported bladder injuries were fistulas, giving an incidence of vesicovaginal fistula of 0.8 of 1000 procedures after all hysterectomies: 2.2 of 1000 after laparoscopic, 1.0 of 1000 after total abdominal, 0 of 1000 after supracervical abdominal, and 0.2 of 1000 after vaginal hysterectomy. Difficulties during an operation with a bladder injury were encountered in 53%, 37%, 100%, and 0%; the failure rates of primary repair of a simple bladder injury were 5%, 18%, 0%, and 0%; the failure rates of primary repair of a vesicovaginal fistula were 17%, 20%, 0%, and 0%; and the convalescence times after a bladder injury were 51 days, 118 days, 71 days, and 99 days after laparoscopic, abdominal, supracervical abdominal, and vaginal hysterectomy, respectively. Conclusion The risk of ureteral injury is higher after laparoscopic hysterectomy compared with traditional hysterectomies.

Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995–2006

BACKGROUND The number of children born after frozen embryo transfer (FET) is steadily rising. However, studies on obstetric and perinatal outcomes are limited. Our primary aim was to compare the perinatal health of children born after FET and fresh embryo transfer, and to use data from children born after spontaneous conception as a reference. METHODS In a register-based cohort study we evaluated the obstetric and perinatal outcomes of children born after FET (n = 2293), fresh embryo transfer (n = 4151) and those born after spontaneous pregnancy (reference group; n = 31 946). Data were collected from the registers of two infertility outpatient clinics, two university hospitals and the Finnish Medical Birth Register (1995-2006). RESULTS After adjusting for confounding factors the FET group showed decreased risks of preterm birth [adjusted odd ratio (AOR) 0.83, 95% confidence interval (CI) 0.71-0.97], low birthweight (AOR 0.74; 0.62-0.88) and being small for gestational age (AOR 0.63; 0.49-0.83) compared with the fresh embryo transfer group. Mean birthweight was 134 g higher in the FET singletons versus the fresh embryo transfer singletons (P< 0.0001). When FET singletons were compared with the reference group, increased risks of preterm birth (AOR 1.45; 1.25-1.68) and low birthweight (AOR 1.22; 1.03-1.45) and a decreased risk of being small for gestational age (AOR 0.71; 0.54-0.92) were found. No excess of perinatal and infant mortality occurred between the groups. CONCLUSIONS Embryo freezing does not adversely affect perinatal outcome in terms of prematurity, low birthweight and being small for gestational age versus the fresh embryo transfer and the outcome is similar or even better, particularly regarding fetal growth. Our study, which is one of the largest on FET pregnancies, provides further evidence on the safety of FET.

A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients

OBJECTIVE Phytoestrogens are popular in treatment of menopause, although scientific evidence is insufficient as to their efficacy. We studied the effects of daily use of isoflavonoids on climacteric symptoms and quality of life in patients with a history of breast cancer. METHODS Sixty-two postmenopausal symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for 3 months; the treatment regimens were reversed after a 2-month washout period. Fifty-six women completed the study. Menopausal symptoms were recorded on the Kupperman index and the visual analogue scale, and working capacity and mood changes were assessed via validated questionnaires. In addition, we followed the levels of phytoestrogens, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and sex hormone–binding globulin. Liver enzymes and creatinine were also assessed at each visit. RESULTS The phytoestrogen regimen raised the circulating levels of phytoestrogens (daidzein, genistein, equol) 19- to 106-fold. The Kupperman index was reduced by 4.2 ± 9.6 (mean ± standard deviation) (15.5%) during phytoestrogen use and similarly by 4.0 ± 8.1 (14.7%) during placebo use (P nonsignificant). The quality of life parameters (working capacity, mood changes) were unaffected by phytoestrogen. In addition, the phytoestrogen regimen caused no changes in FSH, LH, estradiol, or sex hormone-binding globulin. Phytoestrogen treatment was well tolerated and caused no changes in liver enzymes, creatinine, body mass index, or blood pressure. Of the 56 women, 25 (44.6%) preferred the phytoestrogen regimen, 15 preferred the placebo (26.8%), and 16 (28.6%) reported no preference (nonsignificant). CONCLUSION Pure isoflavonoids did not alleviate subjective menopausal symptoms in breast cancer patients.

Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group

STUDY QUESTIONS What are the risks of adverse outcomes in singletons born after frozen-thawed embryo transfer (FET)? SUMMARY ANSWER Singletons born after FET have a better perinatal outcome compared with singletons born after fresh IVF and ICSI as regards low birthweight (LBW) and preterm birth (PTB), but a worse perinatal outcome compared with singletons born after spontaneous conception. WHAT IS KNOWN ALREADY Previous studies have shown a worse perinatal outcome in children born after IVF in general compared with children born after spontaneous conception. In singletons born after FET, a lower rate of PTB and LBW and a higher rate of large for gestational age (LGA) compared with singletons born after fresh IVF have been shown. STUDY DESIGN A retrospective Nordic population-based cohort study of all singletons conceived after FET in Denmark, Norway and Sweden until December 2007 was performed. PARTICIPANTS/MATERIALS, SETTING AND METHODS Singletons born after FET (n = 6647) were compared with a control group of singletons born after fresh IVF and ICSI (n = 42 242) and singletons born after spontaneous conception (n = 288 542). Data on perinatal outcomes were obtained by linkage to the national Medical Birth Registries. Odds ratios were calculated for several perinatal outcomes and adjustments were made for maternal age, parity, year of birth, offspring sex and country of origin. MAIN RESULTS AND THE ROLE OF CHANCE Singletons born after FET had a lower risk of LBW (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI) 0.71-0.91), PTB (aOR 0.84, 95% CI 0.76-0.92), very PTB (VPTB; aOR 0.79, 95% CI 0.66-0.95) and small for gestational age (SGA; aOR 0.72, 95% CI 0.62-0.83), but a higher risk of post-term birth (aOR 1.40, 95% CI 1.27-1.55), LGA (aOR 1.45, 95% CI 1.27-1.64), macrosomia (aOR 1.58, 95% CI 1.39-1.80) and perinatal mortality (aOR 1.49, 95% CI 1.07-2.07) compared with singletons born after fresh IVF and ICSI. Compared with children conceived after spontaneous conception, singletons born after FET had a higher risk of LBW (aOR 1.27, 95% CI 1.13-1.43), very LBW (aOR 1.69, 95% CI 1.33-2.15), PTB (aOR 1.49, 95% CI 1.35-1.63), VPTB (aOR 2.68, 95% CI 2.24-3.22), SGA (aOR 1.18, 95% CI 1.03-1.35), LGA (aOR 1.29, 95% CI 1.15-1.45), macrosomia (aOR 1.29, 95% CI 1.15-1.45) and perinatal (aOR 1.39, 95% CI 1.03-1.87) neonatal (aOR 1.87, 95% CI 1.23-2.84) and infant mortality (aOR 1.92, 95% CI 1.36-2.72). When analyzing trends over time, the risk of being born LGA increased over time for singletons born after FET compared with singletons born after fresh IVF and ICSI (P = 0.04). LIMITATIONS, REASONS FOR CAUTION As in all observational studies, the possible role of residual confounding factors and bias should be considered. In this study, we were not able to control for confounding factors, such as BMI, smoking and reason for, or length of, infertility. WIDER IMPLICATIONS OF THE FINDINGS Perinatal outcomes in this large population-based cohort of children born after FET from three Nordic countries compared with fresh IVF and ICSI and spontaneous conception were in agreement with the literature.

Elective single-embryo transfer in women aged 40–44 years

STUDY QUESTION Is an elective single-embryo transfer (eSET) policy feasible for women aged 40 or older? SUMMARY ANSWER For older women (aged 40-44 years) with a good prognosis, an eSET policy can be applied with acceptable cumulative clinical pregnancy rates and live birth rates. WHAT IS KNOWN ALREADY Various studies have shown the effectiveness of eSET in women aged <35 years with high cumulative pregnancy rates and low rates of multiple births. STUDY DESIGN, SIZE, DURATION This retrospective cohort study included 628 women treated between 2000 and 2009. PARTICIPANTS, SETTING, METHODS Women aged 40-44 years underwent a fresh cycle of IVF or ICSI treatment with eSET (n = 264) or double-embryo transfer (DET) (n = 364). In the subsequent frozen-thawed embryo transfer cycles, SET/DET was performed in both groups according to the number of embryos available and the opinion of the couple. The study was performed at the Family Federation of Finland Helsinki Fertility Clinic. MAIN RESULTS AND THE ROLE OF CHANCE In the fresh cycles, the clinical pregnancy rates were 23.5 and 19.5% in the eSET and DET groups, respectively, and live birth rates were 13.6 and 11.0%, respectively. In the fresh cycles with eSET, there were no twin pregnancies, but in the DET group, there were three sets of twins (7.5%). The cumulative clinical pregnancy rates per oocyte retrieval were 37.1 and 24.2% in the eSET and DET groups, respectively (P < 0.001), and the cumulative live birth rates were 22.7 and 13.2%, respectively (P = 0.002). Cumulative twin rates were 6.7% (n = 4) in the eSET group and 8.3% (n = 4) in the DET group (P = 0.726). All of the twin pregnancies in the eSET group resulted from frozen and thawed DET embryo transfer cycles. LIMITATIONS The characteristics of the two patients groups are not comparable because the suitability of eSET was individually assessed by a clinician based on both clinical prognostic factors and the outcome of IVF or ICSI, i.e. the number and quality of embryos. WIDER IMPLICATIONS OF THE FINDINGS This study may be generalized to IVF units having experience in eSET and cryopreservation.

A Systematic Evaluation of Factors Associated With Nocturia—The Population-based FINNO Study

In a case-control study with prevalence sampling, the authors explored the correlates for nocturia and their population-level impact. In 2003–2004, questionnaires were mailed to 6,000 subjects (aged 18–79 years) randomly identified from the Finnish Population Register (62.4% participated; 53.7% were female). Questionnaires contained items on medical conditions, medications, lifestyle, sociodemographic and reproductive factors, urinary symptoms, and snoring. Nocturia was defined as ≥2 voids/night. In age-adjusted analyses, factors associated with nocturia were entered into a multivariate model. Backward elimination was used to select variables for the final model, with adjustment for confounding. Although numerous correlates were identified, none affected ≥50% of nocturia cases of both sexes. The factors with the greatest impact at the population level were (urinary) urgency (attributable number/1,000 subjects (AN) = 24), benign prostatic hyperplasia (AN = 19), and snoring (AN = 16) for men and overweight and obesity (AN = 40), urgency (AN = 24), and snoring (AN = 17) for women. Moreover, correlates included prostate cancer and antidepressant use for men, coronary artery disease and diabetes for women, and restless legs syndrome and obesity for both sexes. Although several correlates were identified, none accounted for a substantial proportion of the population burden, highlighting the multifactorial etiology of nocturia.

Assisted reproductive technology in Europe, 2012: results generated from European registers by ESHRE.

STUDY QUESTION The 16th European IVF-monitoring (EIM) report presents the data of the treatments involving assisted reproductive technology (ART) and intrauterine insemination (IUI) initiated in Europe during 2012: are there any changes compared with previous years? SUMMARY ANSWER Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year, the pregnancy rates (PRs) in 2012 remained stable compared with those reported in 2011, and the number of transfers with multiple embryos (3+) and the multiple delivery rates were lower than ever before. WHAT IS KNOWN ALREADY Since 1997, ART data in Europe have been collected and re-ported in 15 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE). Data for cycles between 1 January and 31 December 2012 were collected from National Registers, when existing, or on a voluntary basis by personal information. PARTICIPANTS/MATERIALS, SETTING, METHODS From 34 countries (+1 compared with 2011), 1111 clinics reported 640 144 treatment cycles including 139 978 of IVF, 312 600 of ICSI, 139 558 of frozen embryo replacement (FER), 33 605 of egg donation (ED), 421 of in vitro maturation, 8433 of preimplantation genetic diagnosis/preimplantation genetic screening and 5549 of frozen oocyte replacements (FOR). European data on intrauterine insemination using husband/partners semen (IUI-H) and donor semen (IUI-D) were reported from 1126 IUI labs in 24 countries. A total of 175 028 IUI-H and 43 497 IUI-D cycles were included. MAIN RESULTS AND THE ROLE OF CHANCE In 18 countries where all clinics reported to their ART register, a total of 369 081 ART cycles were performed in a population of around 295 million inhabitants, corresponding to 1252 cycles per million inhabitants (range 325-2732 cycles per million inhabitants). For all IVF cycles, the clinical PRs per aspiration and per transfer were stable with 29.4 (29.1% in 2011) and 33.8% (33.2% in 2011), respectively. For ICSI, the corresponding rates also were stable with 27.8 (27.9% in 2011) and 32.3% (31.8% in 2011). In FER cycles, the PR per thawing/warming increased to 23.1% (21.3% in 2011). In ED cycles, the PR per fresh transfer increased to 48.4% (45.8% in 2011) and to 35.9% (33.6% in 2011) per thawed transfer, while it was 45.1% for transfers after FOR. The delivery rate after IUI remained stable, at 8.5% (8.3% in 2011) after IUI-H and 12.0% (12.2% in 2011) after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 30.2, 55.4, 13.3 and 1.1% of the cycles, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 82.1, 17.3 and 0.6%, respectively, resulting in a total multiple delivery rate of 17.9% compared with 19.2% in 2011 and 20.6% in 2010. In FER cycles, the multiple delivery rate was 12.5% (12.2% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.0%/0.4% and 7.2%/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS The 16th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 640 000 cycles reported in 2012 with an increasing contribution to birthrate in many countries. However, the need to improve and standardize the national registries, and to establish validation methodologies remains manifest. STUDY FUNDING/COMPETING INTERESTS The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The Finnish Gestational Diabetes Prevention Study (RADIEL): A Randomized Controlled Trial.

OBJECTIVE To assess whether gestational diabetes mellitus (GDM) can be prevented by a moderate lifestyle intervention in pregnant women who are at high risk for the disease. RESEARCH DESIGN AND METHODS Two hundred ninety-three women with a history of GDM and/or a prepregnancy BMI of ≥30 kg/m2 were enrolled in the study at <20 weeks of gestation and were randomly allocated to the intervention group (n = 155) or the control group (n = 138). Each subject in the intervention group received individualized counseling on diet, physical activity, and weight control from trained study nurses, and had one group meeting with a dietitian. The control group received standard antenatal care. The diagnosis of GDM was based on a 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. RESULTS A total of 269 women were included in the analyses. The incidence of GDM was 13.9% in the intervention group and 21.6% in the control group ([95% CI 0.40–0.98%]; P = 0.044, after adjustment for age, prepregnancy BMI, previous GDM status, and the number of weeks of gestation). Gestational weight gain was lower in the intervention group (−0.58 kg [95% CI −1.12 to −0.04 kg]; adjusted P = 0.037). Women in the intervention group increased their leisure time physical activity more and improved their dietary quality compared with women in the control group. CONCLUSIONS A moderate individualized lifestyle intervention reduced the incidence of GDM by 39% in high-risk pregnant women. These findings may have major health consequences for both the mother and the child.

Female fertility and childbirth after ileal pouch–anal anastomosis for ulcerative colitis

The aim of this study was to calculate the probability of becoming pregnant after ileal pouch–anal anastomosis (IPAA) for ulcerative colitis, and to evaluate complications during pregnancy and childbirth.

Transvaginal Doppler study of uterine artery blood flow in in vitro fertilization-embryo transfer cycles

OBJECTIVE To verify whether uterine artery impedance, measured as pulsatility index and resistance index is related to the outcome of in IVF-ET cycles. DESIGN Prospective study of infertile women participating in an IVF-ET program. SETTING University Hospital. PATIENTS Two hundred women (24 to 40 years of age), who had one to three good quality embryos transferred to the uterus after a standardized IVF cycle. INTERVENTION Transvaginal color Doppler and a blood sample on the day of ET. MAIN OUTCOME MEASURES Uterine artery pulsatility index and resistance index, endometrial thickness, serum E2 and P concentrations, clinical pregnancy rate (PR). RESULTS Pulsatility indices and resistance indices were lower in conception (2.45 +/- 0.54 and 0.85 +/- 0.04, respectively) than in nonconception cycles (2.66 +/- 0.39 and 0.87 +/- 0.04, respectively), although the overlap of the values is considerable. Overall PR was 35% per ET, and it decreased significantly when pulsatility index was > 3.0 (15%) and resistance index > 0.92 (13%), being lowest when pulsatility index was > 3.3 and resistance index > 0.95 (10%). Such a high impedance was detected in 9% of nonconception cycles. CONCLUSION In IVF-ET cycles the uterus is likely to be unreceptive when uterine artery pulsatility index is > 3.3 and resistance index > 0.95 before ET, but this occurs only in 9% of the cycles.