Anssi Tenhunen

Diagnosis of luteinized unruptured follicle (LUF) syndrome by ultrasound

To evaluate the role of ultrasound in diagnosing luteinized unruptured follicle (LUF), 37 women with unexplained infertility were examined for two to three menstrual cycles. Laparoscopy or laparotomy was performed on days 16 to 18 of the third study cycle in 25 patients. The LUF syndrome was suspected at ultrasound examination in 57 of 100 cycles observed. In the remaining 43 cycles, follicular collapse was observed in 33, and 10 were diagnosed as anovulatory. At laparoscopy or laparotomy on 25 patients, 18 of the 21 patients diagnosed as having LUF by ultrasound had a corpus luteum without a stigma. The other three cases diagnosed as LUF by ultrasound had ovulation stigmata. Additional findings in the 25 patients who underwent laparotomy or laparoscopy were endometriosis in 7 (5 of whom had LUF as well), ovulation in 5, bilateral hydrosalpinx in 1, and inability to visualize the ovaries because of adhesions in 1. The LUF syndrome was not a consistent change in the ovulatory pattern of most of the patients. It occurred by ultrasound diagnosis in three consecutive cycles in only 34% of patients.

Pregnancy proteins in seminal plasma, seminal vesicles, preovulatory follicular fluid, and ovary.

A number of proteins previously thought to be specific for the placenta or pregnancy have been identified in the fluids bathing both the oocyte and the sperm. In many cases their concentrations in follicular fluid and seminal plasma greatly exceeded those in the serum of nonpregnant women or men, and sometimes they even exceeded the levels in pregnancy sera. We report here the occurrence of PP5, PP12, PP14 and PAPP-A in follicular fluid and seminal plasma. In follicular fluid, the levels of PP5, PP12, and PAPP-A correlate with the estrogen concentration of the same fluid, and the PP12 and PAPP-A levels also bear a positive correlation to the progesterone concentration. The levels of PP12 and PAPP-A increase as the follicle grows, as do the levels of many steroid hormones. Therefore, the apparent correlations observed may be merely coincidental. However, circumstantial evidence from other reproductive organs indicates that the synthesis of PP12 and PAPP-A is stimulated by progesterone. Results of immunohistochemical staining show that PP12 and PAPP-A are localized in the luteinized granulosa cells and the corpus luteum. Previous studies indicate that PP5 and PAPP-A inhibit the action of proteolytic enzymes plasmin and elastase, which are believed to be involved in the mechanisms of ovulation. The study of the significance of these various placental proteins for human reproduction is only at its beginning. Clearly, elucidation of their function is the key to a more fundamental understanding of their role in the events governing ovulation and implantation.

Ovarian electrocauterization causes LH-regulated but not insulin-regulated endocrine changes.

OBJECTIVE We studied the effects of ovarian electrocauterization on the serum levels of luteinizing hormone (LH), testosterone, insulin, sex hormone‐binding globulin (SHBG) and insulin‐like growth factor binding globulin‐1 (IGFBP‐1) in women with polycystic ovarian disease (PCOD).

Conservative treatment of ectopic pregnancy.

As a conservative nonsurgical treatment of an early ectopic pregnancy, local prostaglandin, parenteral or local methotrexate, local hyperosmolar glucose, and also expectant management have been used successfully in selected cases. The success rate of conservative treatment has been 71%-100% and that of tubal patency after different kinds of conservative treatment 72-93% of patients. In the present study of expectant management in early ectopic pregnancy in patients with decreasing serum hCG levels, spontaneous resolution was observed in 64.6% of patients and in the total series of 207 ectopic pregnancies in 15.0% of patients. Expectant management of early ectopic pregnancy is recommended when emergency surgery is not needed on admission and the serum hCG level is decreasing as noted in two consecutive estimations with an interval of 1-2 days.

Follicular fluid prostaglandins in endometriosis and ovarian hyperstimulation

To study the presence of prostaglandin F2 alpha (PGF2 alpha), prostacyclin (PGI2), and thromboxane A2 (TxA2) in the human ovary, follicular fluid samples were collected with puncture at laparoscopy in 17 women with pelvic endometriosis, 17 women with tubal occlusion and healthy ovaries, and 5 women with tubal occlusion and induced ovarian hyperstimulation between menstrual cycle days 8 and 18. The concentrations of the metabolites of PGF2 alpha, PGI2, and TxA2, i.e., 13,14-dihydro-15-keto PGF2 alpha (M-PGF2 alpha), 6-keto PGF1 alpha, and TxB2, respectively, were measured with radioimmunoassays. Each prostanoid was detected in follicular fluid, but their concentrations were unrelated to the menstrual cycle day at collection. Moreover, these concentrations were similar in various groups of patients. The data suggest that the human ovary produces PGF2 alpha, PGI2, and TxA2 in vivo and that these prostanoids, as measured from follicular fluid, may not be of primary significance in ovulation or endometriosis.

Peritoneal fluid 6-keto-prostaglandin FLα, thromboxane B2 in endometriosis and unexplained infertility

Abstract. To study peritoneal fluid (PF) prostaglandin (PG) in infertile women, 6‐keto‐PGFla (a breakdown product of prostacyclin) and thromboxane B2 (T × B2) (a metabolite of T × A2) were assayed with radio‐immunoassays from PF samples collected at laparascopy from patients with endo‐metriosis (n = 29), unexplained infertility (n = 13) and from women with normal pelvic organs (n = 25). The concentrations of 6‐keto‐PGFla and T×82 in PF were increased (p<0.05) in endometriosis and unexplained infertility, as compared with the corresponding levels in the controls. In patients with endometriosis, both 6‐keto‐PGFla and T × B2 increases were related to the severity of the disease. There was no relationship between 6‐keto‐PGF1α × B2 in PF, and day of menstrual cycle. It is suggested that endometriotic tissue and peritoneal macrophages may contribute to these prostanoids in PF. The smooth muscle activities of PF prostacyclin and T × A2 may be involved in infertility by interfering with tuba1 function.

The occurrence of relaxin in hyperstimulated human preovulatory follicles collected in an in vitro fertilization program

The avidin-biotin immunoperoxidase method and antisera against highly purified porcine relaxin were utilized to localize relaxin-like immunoreactivity in biopsied specimens from six preovulatory follicles from four women undergoing laparoscopy for oocyte retrieval in an in vitro fertilization program. By histological criteria, three of the follicles were luteinized and three were not. Relaxin was found in the granulosa cells of those cells which showed histological luteinization, whereas no relaxin was found in the nonluteinized preovulatory follicles. Our results show, for the first time, the occurrence of relaxin in the human ovary before ovulation and they suggest that the appearance of relaxin is related to the luteinization process.

Expectant management of ectopic pregnancy

Objective To evaluate expectant management in selected cases of ectopic pregnancy. Methods Transvaginal sonography and estimation of serum hCG concentrations were used in the evaluation and follow-up of ectopic pregnancy. Entry criteria for expectant management were: decreasing level of serum hCG, diameter of the ectopic pregnancy less than 4 cm, and no signs of rupture or acute bleeding by vaginal sonography. Results Expectant management was studied in 83 patients, representing 26% of all ectopic pregnancies during a 2-year period. In 57 patients (69%), spontaneous resolution occurred, corresponding to 18% of all ectopic pregnancies. Laparoscopy was performed in 26 because of clinical symptoms or a rise in hCG level after expectant management for 1–18 days. One patient had a tubal rupture requiring tubal resection by laparoscopy. No serious complications occurred. With increasing experience, the rate of expectant management and spontaneous resolution increased during study period. Conclusion Expectant management with repeated vaginal sonography and estimations of serum hCG concentrations is a useful form of treatment for ectopic pregnancy in selected cases.

The in vitro fertilization program in Helsinki.

SummaryIn the in vitro fertilization program at Departments I and II of Gynecology and Obstetrics, University of Helsinki, 57 patients were stimulated with clomiphene and hMG. Follicular growth was monitored by ultrasound and serum estradiol measurements. Laparoscopic follicular puncture was performed 36h after hCG injection. Three hundred seventy-five follicles were punctured and 227 oocytes recovered, representing an oocyte recovery rate of 61%. A total of 130 oocytes (57%) showed evidence of fertilization and 71% of the fertilized oocytes cleaved. Fifty-seven embryo transfers were carried out at the two-to eight-cell stage. Multiple embryos were transferred to 24 patients. Biochemical pregnancies were encountered in two cases; early abortions, 3–5 weeks after implantation, in two cases. One normal ongoing single pregnancy occurred from a transfer of three four-cell embryos.

Hyperstimulated human preovulatory follicular fluid, luteinized cells of unruptured follicles, and corpus luteum contain pregnancy-associated plasma protein A (PAPP-A)**Supported by grants from the Academy of Finland (02/027), the Cancer Society of Finland, and the Sigrid Juselius Foundation.

Radioimmunoassay, gel filtration, and immunoperoxidase methods were used to study the occurrence, properties, and concentration of pregnancy-associated plasma protein A (PAPP-A) in the human ovary and in the follicular fluid from 97 hyperstimulated follicles from 29 infertile women participating in an in vitro fertilization program. At the detection level of 15 micrograms/l, PAPP-A was found in 83 of 97 follicular fluids, the levels ranging from undetectable to 483 micrograms/l (median, 130 micrograms/l). In gel filtration, PAPP-A immunoreactivity of follicular fluid eluted in the same volume as placental PAPP-A, and the dose-response curves of follicular fluid PAPP-A and purified PAPP-A were parallel. The PAPP-A concentration was not affected by prior treatment with a protease inhibitor. Follicular fluid aspirates containing the ovum had a higher PAPP-A concentration than those in which no ovum was detected (P less than 0.01), whereas no difference was found in the PAPP-A concentrations between follicles yielding an ovum which was fertilized and cleaved and those yielding an unfertilizable oocyte. There was a correlation between PAPP-A and estradiol or progesterone concentrations, and between the PAPP-A concentration and the volume of follicular fluid aspirate. In hyperstimulated unruptured follicles, PAPP-A was localized in the luteinized granulosa and theca interna cells, but not if luteinization was not observed. Corpus luteum cells were also PAPP-A positive, whereas unstimulated Graafian follicles were negative. Our results indicate that PAPP-A appears in the hyperstimulated follicle shortly before ovulation and may thus play a part in the early events of human reproduction.