A novel organotypic culture model for normal human endometrium: regulation of epithelial cell proliferation by estradiol and medroxyprogesterone acetate.

BACKGROUND: A novel organotypic culture system was established for modelling the hormonal responses of the normal human endometrium in vitro. METHODS: Endometrial epithelial cells were cultured as glandular organoids within reconstituted extracellular matrix (Matrigel) in tissue culture inserts and stromal cells on plastic below the epithelial compartment. The effects of estradiol (E2) and E2 together with medroxyprogesterone acetate (MPA) on cell proliferation and the expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR) were studied in 10 epithelial-stromal co-cultures and in three parallel monocultures of epithelial organoids. RESULTS: In co-cultures, E2 was shown to increase the percentage of Ki67-positive cells by approximately 2-fold relative to untreated controls. In the presence of MPA, a significant decrease in cell proliferation was detected. Similar results were obtained when the corresponding percentages of Ki67-positive organoids were calculated instead of individual cells. In the absence of stromal fibroblasts, Ki67 epithelial labelling remained below the control value after both hormonal treatments. Epithelial organoids retained their capacity to express estrogen and progesterone receptors in culture. E2 was shown to markedly increase and MPA to down-regulate the expression of PR. The expression of ERalpha was only slightly affected by either hormonal treatment. CONCLUSIONS: The present organotypic model provides a novel in vitro system in which to study the effects of steroids in the normal human endometrium both in terms of cell proliferation and gene expression. The culture system holds promise as a useful method to screen novel steroid compounds and may help to circumvent problems related to the use of animal models.

Sacrospinous ligament fixation for massive genital prolapse in women aged over 80 years.

OBJECTIVE: To assess the feasibility of vaginal sacrospinous ligament fixation for women over 80 years of age with massive vaginal vault or uterovaginal prolapse. DESIGN: Retrospective observational study with long term follow up. SETTING: Department of Obstetrics and Gynaecology, Tampere University Hospital, Finland. SAMPLE: and Methods The study group consisted of 25 women with a mean (SD) [range] age of 83 (3) [80-93] years: 13 had posthysterectomy vaginal vault prolapse and 12 had massive uterovaginal prolapse. All underwent vaginal sacrospinous ligament fixation with repair of pelvic floor relaxation. Women with uterovaginal prolapse also underwent concomitant vaginal hysterectomy. The long term outcome was assessed in 19 women. The mean follow up period was 33 (31) [2-113] months. MAIN OUTCOME MEASURES: Intra- and post-operative morbidity, mortality and recurrence of prolapse. RESULTS: Sixteen of the 25 women (64 %) had no major intra- or post-operative complications. The mean estimated blood loss was 400 (280) mL, and seven women received blood transfusions. Four women (16%) had cardiovascular complications, and one died of pulmonary embolism. All four had a history of vascular disease. One woman had symptomatic recurrence of vault prolapse treated with a vaginal pessary; two women had asymptomatic cystocele and one had an enterocele requiring no treatment. The outcomes were similar for women with or without concurrent vaginal hysterectomy. CONCLUSION: Transvaginal sacrospinous ligament fixation is an effective treatment for massive vaginal vault or uterovaginal prolapse in aged women. Increased blood loss may elevate the risk of cardiovascular complications especially in elderly patients with a history of vascular disease, thus indicating the importance of intraoperative bleeding control.

Morbidity of 10 110 hysterectomies by type of approach.

BACKGROUND: Since the late 1980s, the option of laparoscopic hysterectomy has raised questions about the most suitable approach to hysterectomy. METHODS: To evaluate the influence of the type of approach, in causing or avoiding certain complaints in hysterectomies a prospective nationwide study was conducted comprising all hysterectomies for benign disease performed in Finland during 1996. The primary outcomes of interest were the operation-related morbidity, common surgical details and post-operative complications. RESULTS: A total of 10 110 hysterectomies, including 5875 abdominal, 1801 vaginal and 2434 laparoscopic operations showed a low rate of overall complications, 17.2, 23.3 and 19.0% respectively. Infections were the most common complications with incidences of 10.5, 13.0 and 9.0% in the abdominal, vaginal and laparoscopic group respectively. The most severe type of haemorrhagic events occurred in 2.1, 3.1 and 2.7% in the abdominal, vaginal and laparoscopic group respectively. Ureter injuries were predominant in laparoscopic group [relative risk (RR) 7.2 compared with abdominal] whereas bowel injuries were most common in vaginal group (RR 2.5 compared with abdominal). Surgeons who had performed >30 laparoscopic hysterectomies had a significantly lower incidence of ureter and bladder injuries (0.5 and 0.8% respectively) than those who had performed < or =30 operations (2.2 and 2.0% respectively). A decreasing trend of bowel complications was also seen with increasing experience in vaginal hysterectomies. CONCLUSIONS: This large-scale observational study on hysterectomies provides novel information on operation-related morbidity of abdominal, vaginal or laparoscopic approach. The results support the importance of the experience of the surgeon in reducing severe complications, especially in laparoscopic and vaginal hysterectomies.

Clinical implications of the didelphic uterus: long-term follow-up of 49 cases.

OBJECTIVE: The aim of the study was to evaluate reproductive performance of women with didelphic uterus and to consider possible long-term consequences associated with this uterine anomaly. STUDY DESIGN: Forty-nine women were diagnosed as having a didelphic uterus with a longitudinal vaginal septum at Tampere University Hospital, Finland between 1962 and 1998. The presence of other anomalies, gynecologic disorders, fertility and outcome of pregnancies were reviewed. The long-term clinical implications associated with a didelphic uterus were evaluated during the mean (S.D.) follow-up period of 9.1 (6.3) years. RESULTS: An obstructed hemivagina was found in nine (18%) out of forty-nine cases; eight of these had ipsilateral renal agenesis. A longitudinal vaginal septum was excised in twenty-six (53%) cases, but metroplasty in none. Five (13%) patients had primary infertility. Thirty-four (94%) out of thirty-six women who wanted to conceive had at least one pregnancy, and they produced seventy-one pregnancies; 21% miscarried, and ectopic pregnancy occurred in 2%. The fetal survival rate was 75%, prematurity 24%, fetal growth retardation 11%, perinatal mortality 5. 3%, and cesarean section rate 84%. Pregnancy located more commonly (76%) in the right uterus than in the left. During the follow-up period endometriosis was observed in seven (16%) out of forty-five cases. Ovarian neoplasm was found in four (9%) cases, one of them had ovarian cancer. CONCLUSIONS: Fertility in women with didelphic uterus is not notably impaired. The prognosis of pregnancy is comparatively good, while prematurity and fetal growth retardation indicate meticulous prenatal care. Long-term follow-up did not reveal that didelphic uterus is associated with increased frequency of endometriosis or genital neoplasm.

Assisted reproduction in women with uterine anomalies.

A retrospective analysis was performed to evaluate the reproductive performance of 17 women with uterine anomalies who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and embryo transfer (ET). Eight women had a unicornuate uterus, and two a didelphic uterus. Seven women with a subseptate uterus underwent metroplasty before assisted reproduction. Ten (58.8%) out of 17 women achieved 11 (18.0%) pregnancies out of 61 embryo transfers in 55 stimulated cycles. The implantation rate per embryo was 8/83 (9.6%) for women with a unicornuate uterus, one of 17 (5. 9%) for those with didelphic uterus and four of 48 (8.3%) for those with subseptate uterus. Pregnancy rates per embryo transfer were 19. 4, 11.1 and 19.0%, respectively. Three out of 11 pregnancies were ectopic, three were miscarriages and five were full-term deliveries, two sets of twins. Delivery rate per embryo transfer was 5.0% in patients with unicornuate or didephic uterus and 14.3% in women who had a subseptate uterus operated prior to assisted reproduction. Women with uterine anomalies treated by IVF or ICSI had low implantation rates. Pregnancy in a subseptate uterus which has been previously operated had a trend to end more frequently in delivery than that in a unicornuate uterus or in a didelphic uterus.

Experience with isotonic 2.2% glycine as distension medium for hysteroscopic endomyometrial resection.

The feasibility of performing hysteroscopic endomyometrial resection using isotonic 2.2% glycine as distension medium was studied in 181 consecutive operations. A standard continuous flow loop-resectoscope was used. Distension was achieved by means of a gravity-fed system and glycine flowed out under its own pressure. The mean (+/-SEM) glycine deficit was 160+/-20 ml and in only 7 patients was it >1 liter (maximum 1,800 ml). Only in patients with >1 liter glycine absorption was there a significant decrease in serum sodium level (mean 9 mmol/l), while serum osmolality remained normal. Apart from 1 case of transient nausea, these patients had no sequelae. We experienced isotonic 2.2% glycine as a useful and safe distending medium for operative hysteroscopy.

Limb anomalies among offspring of women with a septate uterus: a report of three cases.

A retrospective analysis of 467 births among 255 women with uterine malformations revealed that three (0.64%) newborns had limb reduction defects. Two women had a subseptate uterus and one a complete septate uterus with a longitudinal vaginal septum. One newborn had a bilateral split hand and split foot, one had absence of left hand and wrist. One infant born without left hand, wrist and one antebrachial bone associated with omphalocele and diaphragmatic hernia died during the neonatal period. An association between severe limb reduction defects and septate uterus is possible, although the mechanism is unclear. The findings indicate a need to evaluate the uterine cavity if a newborn has this invalid defect, and a detailed ultrasound examination of fetal limbs is warranted in a case of a pregnant septate uterus.

Comparison of hysteroscopic endometrial resection and laparoscopic assisted vaginal hysterectomy for the treatment of menorrhagia.

BACKGROUND: To compare the advantages and disadvantages of the two endoscopic procedures, hysteroscopic endometrial resection and laparoscopic assisted vaginal hysterectomy (LAVH), in the treatment of menorrhagia. METHODS: Forty women requiring surgical treatment for menorrhagia underwent LAVH. These women were compared retrospectively with forty women having had endometrial resection for menorrhagia. The operations were performed between November 1991 and February 1995. RESULTS: Operating time, hospitalization and postoperative recovery were significantly shorter with endometrial resection than with LAVH. In the hysteroscopy group amenorrhea or hypomenorrhea was achieved in 80% of cases. Hysterectomy was performed in two cases (5%). In the hysteroscopy group all but three women (92%) were satisfied with the procedure, in the LAVH group all but one (97%). CONCLUSIONS: In the surgical treatment of menorrhagia both procedures are effective. LAVH is associated with a longer recovery period, but it offers a permanent relief of menorrhagia. Even though endometrial resection does not render all women treated amenorrhoic, the satisfaction rate during the follow-up period was high; it is a useful alternative with many short-term benefits.

Unicornuate uterus and rudimentary horn.

OBJECTIVE: To evaluate clinical implications of the unicornuate uterus and rudimentary horn. DESIGN: A retrospective study. SETTING: A university hospital. PATIENT(S): Forty-two women who had a unicornuate uterus with or without rudimentary horn. INTERVENTION(S): The rudimentary horn was removed in 21 cases. MAIN OUTCOME MEASURE(S): Presence of other anomalies, fertility, and outcome of pregnancies were studied. RESULT(S): A right unicornuate uterus with noncommunicating rudimentary horn was the most common type of uterine anomaly. Unilateral renal agenesis was found in 13 (38%) of 34 cases. Six (14%) of the 42 patients had primary infertility. Thirty-four women produced 93 pregnancies; ectopic pregnancy (EP; rudimentary horn, tubal) occurred in 20 of these cases (22%). The pregnant uterine horn ruptured in 3 of 7 cases. Eight (57%) of the 14 women with infertility underwent treatment by IVF-ET; 4 of them conceived, and 2 had term delivery. The fetal survival rate was 61%, prematurity 17%, fetal growth retardation 5%, and the spontaneous intrauterine (IU) abortion rate was 16%. Pregnancy-induced hypertension (PIH) was more common in women lacking a kidney than in those with two kidneys. CONCLUSION(S): The high number of EPs indicates removal of rudimentary horn and its tube when diagnosed. The prognosis of IU pregnancy is not impaired in the unicornuate uterus although prematurity threatens. Unilateral renal agenesis is associated with PIH.

Reproductive performance of women with uterine anomalies after abdominal or hysteroscopic metroplasty or no surgical treatment.

STUDY OBJECTIVE: To evaluate reproductive performance in women with a confirmed uterine anomaly treated by abdominal or hysteroscopic metroplasty, or by no surgical procedure. DESIGN: Retrospective study. SETTING: A university hospital. PATIENTS: Four hundred four women with uterine anomaly, of whom 247 had complete or partial septate uterus or partial bicornuate uterus. INTERVENTIONS: Hysteroscopic metroplasty was performed in 32 patients with septate or subseptate uterus. Twenty women underwent abdominal metroplasty (Jones or Tompkins procedure) and 140 had no operative treatment. MEASUREMENTS AND MAIN RESULTS: Fetal survival improved from 13% to 91% after hysteroscopic metroplasty and from 3% to 86% after the abdominal procedure. A living child was born in 67% of 264 pregnancies in 116 women with septate uterus with no surgical treatment. When 19 patients with hysteroscopic metroplasty were matched by age, gravidity, and type of uterine anomaly with 19 women not subjected to metroplasty, the rates were 86% and 68%, respectively (p = 0.089). CONCLUSIONS: Hysteroscopic metroplasty has replaced abdominal metroplasty in the treatment of septate uterus. It improves the fetal survival rate in women with repeated miscarriage. It does not enhance pregnancy rates in infertile women with septate uterus, but as a minimally invasive uterine repair, it may be carried out before assisted reproduction. Pregnancy in the septate uterus can also progress without any surgical treatment. Metroplasty seems to prevent breech delivery and to decrease the cesarean section rate, which are potential benefits.

Placental glucose transporters in fetal intrauterine growth retardation and macrosomia.

To investigate the role of placental glucose delivery in fetal growth, two glucose transporters (Glut3 and Glut4) were determined from term placentae. This was accomplished by immunoblotting from crude placental membrane samples from cases of fetal intrauterine growth retardation (IUGR, n = 6), macrosomia (n = 6), maternal diabetes mellitus (n = 4) and normal term (n = 8). Glut3 and Glut4 were detected in only very low numbers in all patient groups and there were no changes in their placental density, which suggests that the expression of these transporters is not involved in disorders of fetal growth. However, birth weight corresponded to placental weight, indicating that the total amount of Glut3 and Glut4 is reduced in IUGR and increased in macrosomia.

Finnish national register of laparoscopic hysterectomies: a review and complications of 1165 operations.

OBJECTIVE: We evaluated the advantages and disadvantages of laparoscopic hysterectomy over a 2-year period when this new technique was introduced to several hospitals in Finland. STUDY DESIGN: A nationwide register was founded and a prospective multicenter survey of 1165 laparoscopic hysterectomies was carried out from January 1993 to December 1994. The operations were performed because of uterine fibroids (54%), menorrhagia (27%), dysmenorrhea (8%), endometriosis (2%), and other reasons (9%) by 68 gynecologists at 30 hospitals. RESULTS: The mean operation time was 132 minutes. The patients stayed in hospital for an average of 3.3 days, and the mean convalescence period was 17.9 days, half that after abdominal hysterectomy. Complications occurred in 10.2% of the procedures: infections in 5.6%, vascular complications in 1.2%, urinary tract complications in 2.7%, and bowel complications in 0.4%. CONCLUSIONS: Laparoscopic hysterectomy offers a short hospital stay and convalescence time to the patient, but effective teaching is imperative to minimize, in particular, the risk of urinary tract injuries.

Infertility and coeliac disease.

BACKGROUND: Coeliac women may suffer from gynaecological and obstetric complications. It is possible that these complications are the first symptom of coeliac disease. AIMS: To investigate the occurrence of subclinical coeliac disease in patients with infertility or recurrent miscarriages. SUBJECTS: Women of reproductive age who were attending the hospital because of either primary or secondary infertility, or two or more miscarriages. Women undergoing sterilisation served as control subjects. METHODS: The diagnostic investigation for infertility included the endocrine status, diagnostic laparoscopy, investigation of tubal patency, postcoital test, and semen analysis of the partner. Circulating antibodies against IgA class reticulin and gliadin were used in screening for coeliac disease. In positive cases, the diagnosis was confirmed by small bowel biopsy specimens. RESULTS: Four (2.7%) of 150 women in the infertility group, and none of the 150 control subjects were found to have coeliac disease (p = 0.06). All four women with coeliac disease suffered from infertility of unexplained origin. Altogether 98 women had no discoverable reason for infertility. Thus, in this subgroup the frequency of coeliac disease was 4.1% (four of 98), the difference from the control group being statistically significant (p = 0.02). None of the coeliac women had extensive malabsorption, but two had iron deficiency anaemia. One women with coeliac disease has had a normal delivery. None of the 50 women with miscarriage had coeliac disease. CONCLUSION: Patients having fertility problems may have subclinical coeliac disease, which can be detected by serological screening tests. Silent coeliac disease should be considered in the case of women with unexplained infertility.

Polymerase chain reaction assay with urine specimens in the diagnosis of acute chlamydia trachomatis infection in women.

OBJECTIVE: The purpose of this study was to evaluate the benefits achievable by Amplicor polymerase chain reaction (PCR) (F. Hoffmann-LaRoche Ltd., Basel, Switzerland) with urine specimens in addition to PACE 2 (Gen-Probe, Inc., San Diego, California) assay with cervical swab specimens in the diagnosis of Chlamydia trachomatis in women. METHODS: Cervical and urine specimens from 286 women were tested for C. trachomatis by PACE 2 and Amplicor PCR, respectively. All urine specimens were analyzed undiluted and diluted 1:10 to detect and eliminate possible PCR inhibition. A confirmatory PCR assay using major outer membrane protein-based primers (MOMP-PCR) was used on urine specimens that were positive by PCR from women who were negative by PACE 2 with cervical swab specimens. RESULTS: Of the endocervical specimens, 26 were positive by the PACE 2 assay. The PCR with urine was positive in 21 of these patients. When the urine specimens were analyzed diluted 1:10, 4 of the 5 PCR-negative specimens from PACE 2-positive patients turned positive by the PCR. Additionally, 4 urine specimens from PACE 2-negative women were positive by the PCR with urine, and 3 of them could be confirmed by MOMP-PCR. Altogether, 29 women were found to be positive for C. trachomatis by either of the two assays. CONCLUSIONS: By using the PCR with urine specimens, an 11% increase in sensitivity could be achieved in addition to that obtained by PACE 2 assay with cervical swab specimens. In the present material, however, the increased sensitivity was reversed by the presence of PCR inhibitors in 14% of the female urine specimens. Amplicor PCR with urine specimens can undoubtedly be recommended for the diagnosis of chlamydial infections in women. However, constant monitoring of the PCR inhibition seems highly advisable to obtain full benefit of the sensitivity of the PCR.

Outcome of pregnancies in women with treated or untreated hyperprolactinemia.

The outcome of 103 pregnancies in 64 women with constant hyperprolactinemia was evaluated. Seventy-eight pregnancies had been induced with bromocriptine and 25 occurred without any treatment. In all, 66% of the pregnancies ended in delivery, 17% in miscarriage, 10% in tubal pregnancy and 7% in induced abortion. The pregnancy of women with untreated hyperprolactinemia was more frequently ectopic when compared to those in women treated by bromocriptine. Obstetric complications as well as signs of tumoral enlargement during pregnancy were rare in hyperprolactinemic women treated or untreated with bromocriptine. Untreated hyperprolactinemia as a risk factor in tubal pregnancy is proposed.