Hans Bokström

Livebirth after uterus transplantation

BACKGROUND Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported. METHODS In 2013, a 35-year-old woman with congenital absence of the uterus (Rokitansky syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. In-vitro fertilisation treatment of the recipient and her partner had been done before transplantation, from which 11 embryos were cryopreserved. FINDINGS The recipient and the donor had essentially uneventful postoperative recoveries. The recipients first menstruation occurred 43 days after transplantation and she continued to menstruate at regular intervals of between 26 and 36 days (median 32 days). 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (tacrolimus, azathioprine, and corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a caesarean section was done because of abnormal cardiotocography. A male baby with a normal birthweight for gestational age (1775 g) and with APGAR scores 9, 9, 10 was born. INTERPRETATION We describe the first livebirth after uterus transplantation. This report is a proof-of-concept for uterus transplantation as a treatment for uterine factor infertility. Furthermore, the results show the feasibility of live uterus donation, even from a postmenopausal donor. FUNDING Jane and Dan Olsson Foundation for Science.

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women with preterm prelabor rupture of membranes

Background.  Previous studies have shown an association between intra‐amniotic microbial invasion and/or inflammation and spontaneous preterm birth. The aim of this study was to investigate the occurrence of intra‐amniotic microorganisms and cytokines [interleukin (IL)‐6 and IL‐8] in a Swedish population, with low incidence of preterm birth, of women with preterm prelabor rupture of membranes and their correlation to preterm birth.

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women in preterm labor

Background. Previous studies indicate an association between intra‐amniotic microbial invasion and/or inflammation and spontaneous preterm birth, but there is a limited amount of data available from Europe. The aim of this study was to investigate the occurrence of intra‐amniotic microorganisms and cytokines (interleukin‐6 and interleukin‐8) in a Swedish population of women in preterm labor and their correlation with preterm birth.

Ectopic pregnancy: in vitro effects of prostaglandins on the oviduct and corpus luteum*

An in vitro model for evaluation of pharmacologic treatment of ectopic pregnancy (EP) was designed. In cases of EP, specimens from the tubal wall, the tubal artery, and the corpus luteum capsule were used for contractility studies. In addition, tissue slices from the corpus luteum of EP were incubated for determination of progesterone production. In vitro administration of prostaglandin F2 alpha (PGF 2 alpha) induced a marked increase in activity of the tubal muscle and pronounced constriction of the tubal artery. PGF2 alpha also reduced the human chorionic gonadotropin-induced increase in progesterone production from the corpus luteum. PGE2 conversely, inhibited the tubal muscle activity and had a moderate constrictive effect on the tubal artery. Furthermore PGE2 increased the progesterone formation from the corpus luteum. In theory, the demonstrated in vitro effects indicate that as opposed to PGE2 compounds, PGF2 alpha compounds may be useful for pharmacologic treatment of EP.

Preoperative Dilatation of the Cervix at Legal Abortion with a Synthetic, Fast-Swelling Hygroscopic Tent

Preoperative dilatation of the cervix at first trimester legal abortion has been shown to facilitate the vacuum aspiration procedure and to reduce per‐and postoperative complications as well as late sequelae. The present study represents a clinical trial in which a new synthetic hygroscopic tent, Dilapan®, has been evaluated. Dilapan tents of different diameters with different durations of cervical exposure were tested on a case material of 450 nulliparous women. It was found that treatment with 4 mm tents during 3–4 h or 3 mm tents during 16–20 h produced a cervical dilatation that allowed an easy evacuation of the uterus with a minimum of complications. The advantage of this particular tent is its property of rapid swelling.

Preoperative cervical softening before first trimester legal abortion by mifepristone and misoprostol : A double-blind, randomized, clinical, biochemical, and immunohistochemical study

Abstract Oral administration of the progesterone receptor antagonist mifepristone, as well as the synthetic prostaglandin analog, misoprostol, have been shown to reduce cervical resistance to dilation in connection with legal abortion. The present study is a prospective, randomized study of 45 women comparing the clinical efficacy and possible modes of action of these compounds to induce cervical ripening by studying leukocyte populations and collagenolysis in the cervical stroma. A significantly increased amount of cervical dilatation, estimated to be the diameter of the largest Hegar dilator that passed the internal os without resistance, was observed after both mifepristone (200 mg, 48 and 24 h before surgery) and misoprostol (600 μg, 16–20 h before surgery) compared to placebo, with no significant difference between the two preparations noted (mean 6.9 and 5.9 mm vs 4.5 mm, p

Prostaglandin E and F2α Concentration in the Cervical Mucus and Mechanism of Cervical Ripening

OBJECTIVE To study the mechanism of cervical ripening by determination of prostaglandin E (PGE) and F2 alpha (PGF2 alpha) concentrations in cervical mucus during the course of pregnancy. STUDY DESIGN Cervical mucus was collected from 99 pregnant women attending the mother care unit of the department. Women with sexual intercourse within the last 24 hours before sampling and subjects with bacterial vaginosis were analysed separately. RESULTS Eleven women had sexual intercourse within 24 hours before sampling. The concentration of PGE in their cervical mucus was high corresponding to 2000-4000 pg/mg w w lasting for a period of 10-12 hours postcoitally, whereas the levels of PGF 2 alpha only increased slightly. Bacterial vaginosis was accomplished by a slight but significant elevation of PGF2 alpha levels but only of a minor increment of the PGE values. The prostaglandin concentrations in the mucus from the remaining 68 women were for PGE 102.75 +/- 111.51 and for PGF2 alpha 97.54 +/- 82.48 pg/mg w w (mean +/- SD). Although the values were scattered the concentrations remained at approximately the same level throughout pregnancy and there was no tendency towards an increment during the last weeks of pregnancy when cervical maturation is apparent. CONCLUSION Cervical softening seems not to be accomplished by a massive local release of prostaglandins but rather the result of a number of different mechanisms more or less influenced by minor alterations of prostaglandin synthesis and release. Involved in these mechanisms are probably neutrophil-derived collagenases.

Prostaglandin release from human cervical tissue in the first trimester of pregnancy after preoperative dilatation with hygroscopic tents

Preoperative dilatation with hygroscopic tents before first trimester abortion by vacuum aspiration is widely accepted and reduces the risk of early and late complications. A softening effect and a reduced compliance to mechanical dilatation occurs in addition to pure mechanical dilatation of the cervix. If this softening is an effect of local prostaglandin release, however, is unknown. Prostaglandin (PG) release in vitro from cervical biopsies following dilatation in vivo by a synthetic hygroscopic tent (Dilapan) for periods of 4 h and 18 h was compared with that of biopsies from untreated women. No difference was observed between the release of PGE2, PGF2 alpha, or 6-keto-PGF1 alpha. No significant difference was found in the tissue water content between treated and untreated women (83.8% versus 83.2%). Prostaglandins were also extracted from an alternative cervical dilator, Lamicel (a polyvinyl sponge impregnated with magnesium sulfate), and compared with the corresponding values from women pretreated with the cyclooxygenase inhibitor indomethacin before application of the tent. Significantly higher concentrations of PGE2 and PGF2 alpha but not of 6-keto-PGF1 alpha were found in women who had not been indomethacin-treated compared with indomethacin-treated women. Slices of the cervix from non-pregnant women operated upon for benign conditions were divided into an outer stromal layer and an inner layer, including the mucosa, and the PG-release in vitro was measured. The inner layer of the cervix showed a significantly higher release of PGE2 and PGF2 alpha compared with the outer layer. Lamicel treatment before first trimester abortion results in a significant dilatation of the cervix and a reduced compliance to mechanical dilatation, and this study supports the hypothesis that this effect is mediated via a local PG-release from the cervix. It seems reasonable to believe that Dilapan treatment too has the capacity to induce PG-release from the cervix, but this could not be demonstrated in this study, probably because needle biopsies taken mainly from the outer cervical layers were analyzed.

Fetal hemolytic anemia associated with maternal sulfasalazine therapy during pregnancy

A 29 year-old woman with a diagnosis of ulcerative colitis for 11 years was admitted to the Department of Obstetrics in pregnancy week 26. During the whole course of her pregnancy, she had been treated with sulfasalazine (Salazopyrin EN) in a 1-g twicedaily dose. She had had an intrauterine fetal death at 25 weeks of gestation three years earlier. No fetal malformation or chromosomal aberration was found. Two years later she gave birth to a healthy girl at term. During both of these pregnancies she was treated with sulfasalazine. Additional medications during the two pregnancies were folic acid (Folacin) 0.4 mg daily and ferrous sulfate (Duroferon) 100 mg daily. Her blood group was 0 Rh-positive without signs of immunization. The patient became pregnant for the third time while she was on sulfasalazine 1-g twice-daily treatment in addition to folic acid in a daily dose of 0.4 mg. fter 26 weeks of pregnancy, an ultrasound was performed due to high symphysis /fundus level and fetal ascites was discovered. No malformations were found. Amniocentesis with chromosomal analysis showed normal male karyotype. Due to high blood velocity in the fetal middle cerebral artery, there was a suspicion of severe anemia as an explanation of the noted nonimmune hydrops. A chordocentesis was performed which showed a hemoglobin level of 34 g/l and reticulocytes of 22%. Severe anemia was diagnosed and the fetus was treated with intrauterine blood transfusions. During gestational weeks 26 /31, the fetus received in total three intrauterine blood transfusions, and in gestational week 31 the post-transfusion hemoglobin level was 117 g/l. Tests of maternal blood for parvoand cytomegalovirus infections by PCR, and IgG and IgM antibodies were all negative. Kleihauers test of maternal blood for fetomaternal transfusion was negative. No blood group incompatibility was found and DAT test was negative. No signs of hemolytic anemia were found in maternal blood. The limited amount of fetal blood received from chordocentesis showed normal differential white cell count. There was no glucose-6-phosphatedehydrogenase deficiency and no abnormal hemoglobin chains were found on cationic exchange chromatography. The limited amount of fetal blood available did not allow determination of salazopyrine concentration. However, free hemoglobin concentration was 244 mg/l in fetal blood plasma, confirming the diagnosis of fetal hemolytic anemia and an adverse reaction to sulfasalazine was suspected. The sulfasalazine medication was therefore withdrawn and betamethasone therapy 12 /12 mg intramuscular was initiated in week 30 of pregnancy. Due to premature contractions, a cesarean section was performed at 31 weeks of pregnancy. A baby boy with a birth weight of 2,590 g was delivered with an Apgar score of 3-6-7. During cesarean section, 7 l of

Cervical mucus concentration of prostaglandins E2 and F2α after pretreatment with mifepristone in the first trimester of pregnancy

Cervical dilatation and softening after pretreatment with mifepristone are well documented. As this effect is similar to that observed after local application of prostaglandin E2 (PGE2) it is tempting to speculate that the effect of mifepristone is mediated via an increase of the endogenous secretion of prostaglandins from the cervical mucosa. Eighteen healthy women in the first trimester of pregnancy were treated with oral mifepristone (200 mg) 48 and 24 hours before legal abortion by vacuum aspiration and 18 women in the same age of gestation without any pretreatment served as controls. Cervical mucus was collected for measurement of prostaglandins by radioimmunoassay before administration of the drug and in connection with vacuum aspiration. The cervical dilatation at the time of surgery was significantly increased in women given mifepristone as compared with untreated women (7.6 versus 5.8 mm). The wet weight of collected cervical mucus was significantly increased in mifepristone treated women. The amount of PGE2 and prostaglandin F2 alpha per sample was unchanged in mifepristone-treated women, whereas the concentration was lower as an effect of dilution due to an increased yield in cervical secretion observed after mifepristone treatment. The present observation does not give any support to the hypothesis that mifepristone-induced cervical maturation is mediated via an increase in cervical prostaglandin production.