Arterial stiffness during controlled ovarian hyperstimulation and early pregnancy in women exposed to assisted reproduction.

INTRODUCTION: Female sex hormones have vasorelaxing effects in non-pregnant and pregnant women. We aimed to investigate the effect of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF), and early pregnancy, on arterial stiffness as assessed by digital pulse wave analysis (DPA), hypothesizing reduced arterial stiffness as an effect of increased estrogen levels. MATERIAL AND METHODS: A total of 68 women undergoing IVF were examined with DPA before conception and during IVF treatment with COH and embryo transfer (ET), and in gestational week seven in 19 women who became pregnant. Heart rate (HR), mean arterial pressure (MAP) and the DPA variables cardiac ejection elasticity index (EEI), b/a, dicrotic index (DI), d/a and aging index (AI) were measured. RESULTS: HR was significantly increased at all measuring points (p ≤ 0.003) but MAP only at ET (p 0.007). DPA variables representing large arteries (EEI, b/a) and peripheral arteries (DI, but not d/a), and the global variable AI, indicated increased arterial stiffness at ET compared with baseline (p ≤ 0.035). No DPA variable was significantly changed at pregnancy measurements compared to baseline. CONCLUSION: During COH for IVF treatment, DPA showed no changes in arterial stiffness during the follicular phase or in early pregnancy, but increased arterial stiffness in central and peripheral arteries in the early luteal phase. The result suggests a hormonal hemodynamic activation counteracting the effects of estrogen.

Histopathology indicates lymphatic spread of a pelvic retroperitoneal ectopic pregnancy removed by robot-assisted laparoscopy with temporary occlusion of the blood supply.

Retroperitoneal ectopic pregnancies are extremely rare and a diagnostic and therapeutic challenge as an early diagnosis is difficult and all treatments entail a risk for severe bleeding. We present a case of a live completely retroperitoneal ectopic pregnancy in the right obturator fossa. Following 3D color Doppler vaginal ultrasonography to evaluate the relation to larger blood vessels the pregnancy was completely removed by robot-assisted laparoscopic surgery. The hypogastric artery was temporarily occluded by removable vessel clips. Time for surgery was 126 minutes, no bleeding occurred. The postoperative course was uneventful and s-betahCG normalized in five weeks. Histopathology of the intact specimen showed trophoblast surrounded by lymphatic tissue. We believe robot-assisted laparoscopic surgery is a feasible and safe technique for surgery of retroperitoneal ectopic pregnancies with similar or other locations allowing occlusion of the main supplying artery. Lymphatic spread may explain retroperitoneal ectopic pregnancies.

Cumulative delivery rate in an in vitro fertilization program with a single embryo transfer policy.

OBJECTIVE: To investigate the cumulative delivery rate for women completing three fresh embryo transfer cycles or giving birth after the first or second transfer cycle in an in vitro fertilization program with a single embryo transfer (SET) policy. SETTING: Privately run infertility clinic in southern Sweden (Skåne region). POPULATION: Four hundred fifty-three consecutive, unselected public patients beginning an ovum pick-up cycle between July 2002 and June 2004. METHOD: Retrospective, observational study. MAIN OUTCOME MEASURE: Cumulative delivery rates. RESULTS: Of 370 women who completed the study with up to three fresh ET cycles (90% SETs), 244 women (66%) progressed to delivery. Among the deliveries were three sets of twins (1%), one dizygotic. Cumulative delivery rates showed significant differences relative to age <36 (71%) and >or=36 years (47%), and delivery rates relative to rank of ET cycle (first and second vs. third ET cycle - 35, 34, and 21% delivery rates, respectively). CONCLUSIONS: The 66% cumulative delivery rate is in accordance with rates in similar observational studies and in estimation studies, in which predominantly two embryos were used for transfer. The multiple delivery rate was low. We suggest that repeated SET cycles can be implemented on a large scale even in a primarily unselected patient population without compromising the outcome.

Early embryo cleavage and day 2 mononucleation after intracytoplasmatic sperm injection for predicting embryo implantation potential in single embryo transfer cycles.

In this study we analyzed the outcome of 275 fresh single embryo transfer cycles of day 2, mononucleate four-cell preembryos that had either cleaved early (n = 175) or not cleaved early (n = 100) 25 to 28 hours after intracytoplasmatic sperm injection. Neither the implantation rate nor the delivery rate showed any difference between the two groups, indicating that when a top-quality preembryo (mononucleate four-cell preembryo on day 2) is transferred, the presence of early cleavage seems to add no additional advantage in predicting the implantation potential of the preembryo.

A prospective randomized controlled trial comparing two embryo transfer catheters in an ART program.

OBJECTIVE: To compare the performance of the Cook Sydney IVF (SIVF) embryo transfer (ET) catheter and the Edwards-Wallace (EW) ET catheter. DESIGN: Prospective randomized controlled clinical trial with an intention-to-treat analysis. SETTING: Two-center study. PATIENT(S): Four hundred consecutive women <40 years undergoing ET with two fresh embryos. INTERVENTION(S): Women were randomly allocated to undergo ET with either the EW or the SIVF catheter, with possible catheter change in case of insertion difficulties. MAIN OUTCOME MEASURE(S): Live birth and clinical pregnancy rates. RESULT(S): Two hundred two women were allocated to the SIVF catheter and 198 to the EW catheter. No significant differences in the clinical pregnancy rates (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.66-1.47) and live-birth rates (OR 1.09, 95% CI 0.72-1.65) were found. The EW catheter had to be changed more often than the SIVF catheter (OR 9.5, 95% CI 3.3-27.5) because of catheter insertion problems. CONCLUSION(S): The pregnancy and live birth rates were not significantly different with the two catheters, but catheter insertion failure was significantly more common with the EW catheter than with the SIVF catheter.

The probability of successful IVF outcome after poor ovarian response.

BACKGROUND: To evaluate the relationship between age and poor ovarian response to pregnancy and cancellation rate after IVF stimulation. METHODS: Poor ovarian response was defined as 37 years, who were poor responders, had a significantly lower pregnancy rate per OPU (3.0%) compared to normal to high responders in the same age group (22.1%, p<0.05). Also, 43.6% of women >37 years, who were classified as poor responders, did not receive an embryo transfer (ET), compared to 13.2% of normal to high responders in this age group (p<0.05). Poor responders who were 37 years, who receive high doses of FSH have a significantly poorer treatment outcome than can be explained by either age or FSH dose alone. CONCLUSIONS: Poor ovarian response after IVF stimulation requires thorough counselling prior to OPU, regardless of the woman's age. In poor responders >37 years of age, especially those who require high FSH doses, we suggest that the decision whether or not to proceed to OPU should include the couple after thorough counselling, even though the chance of successful outcome is extremely low.

Omega-3 Fatty acids: structure, function, and relation to the metabolic syndrome, infertility, and pregnancy.

Omega-3s are found in oily fish. We have drastically reduced our intake of fish during the last century. Many of us therefore suffer from a deficiency of omega-3s, which has consequences for health. In this review, we focus on structure-functional relationships and the relation of omega-3s to the metabolic syndrome, infertility, and pregnancy.

Nuclear status of four-cell preembryos predicts implantation potential in in vitro fertilization treatment cycles.

OBJECTIVE: To assess the value of routine screening of nuclear status of day-2 four-cell preembryos for single embryo transfer (SET) in predicting implantation. DESIGN: Retrospective analysis. SETTING: Private IVF unit. PATIENT(S): A total of 1,985 fresh embryo transfers on day 2 or day 3 were performed from January 2002 to November 2004. In 1,295 (65.2%) of these transfers, SET was performed. All day-2 four-cell preembryos transferred in SET cycles (n = 861) were analyzed retrospectively for outcome in terms of implantation rate and its relation to the number of visible mononucleate blastomeres (MNBs), the degree of fragmentation, and equality of blastomeres. INTERVENTION(S): Light microscopic evaluation of preembryos before transfer on day 2. MAIN OUTCOME MEASURE(S): Implantation rate. RESULT(S): The number of MNBs was found to be related to implantation, whereas blastomere equality and rate of embryo fragmentation were not. The implantation rate was statistically significantly higher in cycles where a four-cell preembryo with four MNBs was transferred than after transfer of a four-cell preembryo with zero to three MNBs (42% versus 22%). In a logistic regression analysis, nucleation of all blastomeres was the only morphologic parameter that was associated with the implantation rate. CONCLUSION(S): Evaluation of nuclear status of four-cell preembryos is important in predicting implantation potential. Visualization of four MNBs in a four-cell preembryo predicted a statistically significant higher implantation rate than in cases where not all four blastomeres were mononucleate.

Would legislation imposing single embryo transfer be a feasible way to reduce the rate of multiple pregnancies after IVF treatment?

Due to increased maternal and fetal risks, there is a strong opinion in favor of single embryo transfer (SET) in order to reduce the high multiple pregnancy rate after IVF. We have evaluated the effects on pregnancy rate and twinning of recent Swedish legislation on SET. The study comprised three embryo transfer (ET) periods: period I, autumn 2001-spring 2002 (n=609), with a double embryo transfer (DET) policy; period II, autumn 2002 (n=320), a transitional period; and period III, January-September 2003 (n=433), with a SET policy. During the three periods, the SET rates were 25.1, 55.5 and 72.7%, respectively (Kruskal-Wallis test P<0.0001). There was no difference in clinical pregnancy rates (33.3, 32.8 and 37.4%, respectively) (P=0.4), but the twinning rate was significantly lower in the third period (6.2 versus 22.6% in period I and 16.3% in period II) (P<0.005). After introducing a SET policy, the expected decline of twinning was met at an unchanged clinical pregnancy rate. Thus, the SET legislation had no negative consequences for the couples. On the contrary, the lower rate of twinning is expected to reduce the severity and rate of pregnancy complications after IVF. Whether legislation or voluntary SET is the most feasible way to proceed, in order to reduce the multiple pregnancy rates after IVF, can be debated.

[Good results of single embryo transfer after in vitro fertilization. The first follow-up report after the introduction of a new regulatory guideline]. / Goda resultat då endast ett preembryo aterförs efter in vitro-fertilisering. Första konsekvensrapporten sedan ny föreskrift införts.

A legislation was issued by the Swedish National Board of Health from January 1st 2003, stating mandatory single embryo transfer (SET) after in vitro fertilization. Two embryos may, however, be transferred if the risk for twin pregnancy can be considered to be low. Over a period of one year, the rate of SET in our clinic was increased from 25% to 71% of all fresh embryo transfers. In spite of this, we maintained the overall viable pregnancy rate (34%). The twin pregnancy rate, on the other hand, decreased from 23% to 6%. The quality of the transferred embryo(s) was an important factor for success. Transfer of two embryos of good quality did not increase the pregnancy rate compared to transfer of one embryo of good quality but increased the risk for twin pregnancy only.

Women and omega-3 Fatty acids.

Omega-3 fatty acids (omega-3 FA) are constituents of the membranes of all cells in the body and are precursors of locally produced hormones, eicosanoids, which are important in the prevention and treatment of various diseases, especially in women. Omega-3 FA are of interest in some of the most common conditions affecting women. One mechanism underlying dysmenorrhea is a disturbed balance between antiinflammatory, vasodilator eicosanoids derived from omega-3 FA and proinflammatory, vasoconstrictor eicosanoids derived from omega-6 FA. Increased intake of omega-3 FA can reverse the symptoms in this condition by decreasing the amount of omega-6 FA in cell membranes. An increased prostacyclin/thromboxane ratio induced by omega-3 FA can facilitate pregnancy in women with infertility problems by increasing uterine blood flow. Supplementation with omega-3 FA during pregnancy lowers the risk of premature birth and can increase the length of pregnancy and birth weight by altering the balance of eicosanoids involved in labor and promote fetal growth by improving placental blood flow. Intake of omega-3 FA during pregnancy and breast feeding may facilitate the child's brain development. There is also some evidence that supplementation with omega-3 FA might help to prevent preeclampsia, postpartum depression, menopausal problems, postmenopausal osteoporosis, and breast cancer. Furthermore, because elevated triglyceride levels are associated with cardiovascular disease, especially in women; and because omega-3 FA have powerful effects on triglycerides, women in particular gain from an increased intake of these fatty acids. This is especially important in women receiving hormone therapy, which can increase triglyceride levels. The quality of the omega-3 FA preparation is important. It should have an appropriate antioxidant content not to induce lipid peroxidation, and its content of dioxin and polychlorinated biphenyls (PCBs) should be well below the established safe limit.

Structural, functional and circulatory placental changes associated with impaired glucose metabolism.

OBJECTIVE: To investigate associations between structural, functional and circulatory placental changes in pregnancies complicated by impaired glucose metabolism. DESIGN: Umbilical artery (UA) blood flow resistance was measured by Doppler velocimetry in 21 gravidae with diabetes/impaired glucose tolerance (IGT) and 10 healthy gravidae. Umbilical and placental vessel segments were incubated for determination of prostacyclin and thromboxane synthesis, and tissues histologically examined. Non-parametric statistical tests at a two-tailed P<0.05 were used. RESULTS: Placental lesions were more common in diabetes/IGT and, although not being an uniform finding, in general associated with a higher vascular synthesis of thromboxane and/or lower prostacyclin/thromboxane synthesis ratio. As an exception, ischemic villitis was associated with a higher ratio and higher UA flow resistance. CONCLUSIONS: Placental lesions are associated with an altered vascular prostanoid synthesis in diabetes/IGT, but not until structural signs of ischemia develop is a rise of UA blood flow resistance detected.