Pia Saldeen

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 ≤5 follicles at ovum pick up (OPU). Out of 1,706 consecutive OPUs performed during 2003/2004, 290 poor responders were identified. This cohort of poor responders was divided into two groups, ‘older’ and ‘younger’, with a cut‐off at the median age of 37 years. The pregnancy and cancellation rates after OPU were analysed. Results. Women aged >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 had a significantly lower pregnancy rate/OPU compared to normal to high responders who were ≤37 years (14.0 versus 34.5%, p<0.05) and a higher cancellation rate (40.1 versus 10.5%). Logistic regression analyses showed strong correlations between treatment outcome and the number of oocytes, age, and the mean and cumulative FSH dose given. The variable with the strongest impact on negative outcome was an interactive term between mean age and mean‐FSH dose (p = 5.0×10−5), indicating that women >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 womans 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.

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. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to describe the function and actions of omega-3 and omega-6 fatty acids, to outline the potential advantages of omega-3 fatty acid supplementation, and to list the potential sources of omega-3 fatty acids.

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 ≥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.

Association between a low umbilical artery pulsatility index and fetal distress in labor in very prolonged pregnancies.

OBJECTIVE To investigate the association between fetal, umbilical and uterine circulatory changes and adverse perinatal findings in very prolonged pregnancies. STUDY DESIGN 44 women proceeding to 43 completed weeks of gestation with the intention of a trial of vaginal delivery were studied prospectively with ultrasound Doppler velocimetry. An intensified fetal surveillance was routinely commenced at 42 weeks and only uncomplicated pregnancies were allowed to proceed. The endpoint perinatal measures were oligohydramnios, fetal meconium release, fetal distress in labor and birth asphyxia. Flow variables in different groups were compared with the Mann-Whitney U test, Students unpaired t-test, Wilcoxon signed-rank matched-pairs test, Fishers exact test and contingency table analysis, and a two-tailed P value <0.05 was considered statistically significant. RESULTS The umbilical artery pulsatility index was significantly lower in cases of fetal meconium release (n=12) and fetal distress (n=7). The umbilical venous flow velocity was significantly lower in cases of meconium, and the fetal aortic volume flow significantly higher in cases of fetal distress. No significant flow changes were found in connection with oligohydramnios (n=5) and birth asphyxia (n=2). Uterine flow was not significantly affected in any group. CONCLUSIONS In very prolonged pregnancies, fetal distress in labor was not associated with an increased placental vascular resistance. In contrast to previous reports, the umbilical artery pulsatility index was low in cases of fetal distress and meconium release. The etiology is unknown, but a subclinical fetal hypoxia might have triggered a vasodilation of placental vessels. Vasodilation at an unchanged volume flow could also explain the decrease of umbilical venous flow velocity. The increased aortic volume flow indicates an increase of cardiac output in fetuses later developing distress in labor.

Increased synthesis of thromboxane B2 and 6-keto-PGF1α in hand veins from patients with deep venous thrombosis

The production of 6-keto-PGF1 alpha and thromboxane B2 (TxB2) was determined in vitro in hand veins from 35 patients with deep venous thrombosis (DVT), 13 patients with stroke and 14 controls. The TxB2 production was significantly increased, approximately doubled, in patients with DVT and unchanged in patients with stroke. The production of 6-keto-PGF1 alpha was significantly increased in both groups. It is suggested that the increased production of TxB2 might be contributory to thrombosis.

Lack of association between Doppler velocimetry and synthesis of prostacyclin and thromboxane in umbilical cord vessels from growth retarded fetuses

Background. The aim of this study was to investigate the possible association between Doppler velocimetry and synthesis of prostacyclin (PGI2) and thromboxane A2 (TxA2) in umbilical cord vessels. The hypothesis was that an altered balance between PGI2 and TxA2 production is associated with a change of artery flow resistance.

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‐βhCG 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.

Prostanoid production in the umbilicoplacental arterial tree relative to impaired glucose tolerance

The purpose of this study was to investigate prostanoid synthesis in different segments of the umbilicoplacental vascular tree and its relationship to impaired maternal glucose tolerance. Segments from the umbilical artery and vein, allantochorionic artery branches, and the cotyledon artery from 21 women with diabetes or impaired glucose tolerance and 10 healthy women were studied. Production of prostacyclin (PGI2) and thromboxane (TxA2) metabolites was determined. The Mann-Whitney U test, Wilcoxon signed-ranks matched-pairs test, Kruskal-Wallis test, analysis of variance, and simple linear regression analysis were used. A two-tailed P value of < 0.05 was considered statistically significant. From the umbilical artery distal to the cotyledon artery, the PGI2 synthesis decreased and the TxA2 synthesis increased gradually towards the periphery in normal pregnancy. The PGI2/TxA2 ratio was more than 200 times higher in the umbilical artery than in the cotyledon artery. The TxA2 production tended in general to be higher in the diabetic group than in the control group, resulting in significantly lower PGI2/TxA2 ratios in some vessels. The prostanoid production was not significantly correlated to maternal HbA1c or cord C-peptide concentrations. The balance between vascular prostacyclin and thromboxane synthesis in the umbilicoplacental arterial tree changed gradually towards the periphery: the more peripheral, the lower the prostacyclin and the higher the thromboxane production. The physiological role of this phenomenon is unknown, but may be of importance for the equilibration of vascular tone between arteries of different calibers. The altered prostanoid balance found in diabetic pregnancy was not directly attributable to the degree of maternal glycemic control, but may reflect increased free radical activity and peroxide production in diabetes.

The prospects for vaginal delivery in gestations beyond 43 weeks

Objective. To reveal factors influencing the prospect for vaginal delivery in very prolonged pregnancy.

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.