Ljiljana Randić

An immunohistochemical study of leucocytes in human endometrium, first and third trimester basal decidua

An immunohistochemical quantitative study of leucocyte subpopulations on fresh human endometrium and on biopsy specimens of first and third trimester basal decidua in normal (uncomplicated) pregnancies was performed. The most prominent population in endometrial and decidual stroma of basal decidua are macrophages. B cells as well as gamma/delta T cell receptor positive cells were found occasionally, scattered throughout the endometrial/decidual stroma. CD3+ cells were present in a relatively small number in the endometrium as well as in the first trimester basal decidua, but their number was elevated (doubled) in the third trimester of pregnancy. CD2+ cells showed a slight increase in first trimester basal decidua when compared with both endometrium and third trimester basal decidua. Cells with positive NKH-1 marker (CD56+) showed a significant increase in the first trimester, while in the third trimester their number diminished drastically. CD56:CD3 cell ratio increased to more than five times in first trimester basal decidua, while in the third trimester basal decidua decreased drastically. The mentioned increase of CD56+ cells in the first trimester and that of CD3+ cells at term suggests that these cells could have some specific function(s). However, it still has to be established whether the described quantitative changes of decidual leucocytes in basal decidua during pregnancy are of any importance for the mechanism(s) for the fetal allograft protection.

Progesterone Induced Blocking Factor (PIBF) Mediates Progesterone Induced Suppression of Decidual Lymphocyte Cytotoxicity

Laškarin G, Tokmadžić VS, Štrbo N, Bogović T, Szekeres‐Bartho J, Randić L, Podack ER, Rukavina D. Progesterone induced blocking factor (PIBF) mediates progesterone induced suppression of decidual lymphocyte cytotoxicity. AJRI 2002; 48:201–209

Perforin and Fas/FasL cytolytic pathways at the maternal-fetal interface.

The immunogenetic enigma of maternal acceptance of the fetal semiallograft has been termed an immunological paradox. The first trimester decidua is heavily infiltrated with CD56brightCD16− uterine natural killer (uNK) cells which must be prepared to respond to potential pathogen challenges and still be able to control immune responses that allow the development of the fetus. The significant presence of cytolytic mediators, perforin and Fas/Fas ligand (FasL), at the maternal–fetal interface raises a question of their role(s) in the immunological interrelations between maternal tissues and trophoblast cells. As uNK cells in vitro lyse target cell lines (K562, P815 and P815Fas) using these effector molecules, it seems that, although immunocompetent, their cytotoxicity is not directed against trophoblast during normal pregnancy. Therefore, it is generally believed that the hormonal and Th1/Th2 cytokine balance plays an important role in the tolerance and maintenance of pregnancy. This paper gives an overview of the recent findings on the complex immunological events that occur at the maternal–fetal interface.

A three-year evaluation of TCu 380Ag and Multiload Cu 375 intrauterine devices.

A randomized, comparative, multicenter clinical trial of TCu 380Ag and Multiload Cu 375 intrauterine devices (IUDs) was conducted. Safety and acceptability were evaluated through three years following insertion in 884 patients. The two IUDs were similar with respect to all event rates. Thirty-six month life table pregnancy rates were 0.6 per 100 TCu 380Ag users and 1.8 per 100 Multiload Cu 375 users. Continuation rates were 67.4 and 61.4 per 100 users of the respective devices at three years after insertion.

Return to fertility after IUD removal for planned pregnancy

The ability to conceive after discontinuing contraceptive practice is an important concern for women who have not completed their families. This paper focuses on 576 women who had their IUDs removed for planned pregnancy. The data from this study add further evidence that fertility subsequent to IUD removal is not impaired. Among these women followed-up, 94.3% conceived. The majority of these conceptions (55.9%) occurred during the first three months after IUD removal. In addition to analyzing conception rates, there were four factors that were considered in relationship to return to fertility. These were age at removal, duration of use, type of IUD (medicated vs non-medicated) and timing of insertion (interval vs postabortion). Age at removal was the only variable which seemed to influence conception rates.

Short-term Cytolytic Mediators’ Expression in Decidual Lymphocytes is Enhanced by Interleukin-15

We investigated whether decidual adherent cells (DAC) and interleukin (IL)‐15, in comparison to interleukin (IL)‐2 affect cytolytic potential of first trimester decidual lymphocytes (DL).

Chromosome studies in patients with defective reproductive success.

PROBLEM: The objective of this study was to evaluate the contribution of chromosomal anomalies to decreased fertility in humans.
 METHOD OF STUDY: In order to investigate the aetiology of infertility in our population and to assess the karyotype in a group of infertile couples and individuals with fertility problems, 782 persons (259 couples, 158 male and 106 female) with different clinical diagnoses of sterility and infertility were analysed cytogenetically.
 RESULTS: The overall frequency of major chromosomal aberration was 13.1% (103/783), which suggests that fertility or sterility problems in this population are due to chromosomal aberrations. Couples experiencing repeated spontaneous abortions, having malformed children or having sterility problems had chromosomal abnormalities in 18.0% (47/259 couples) of the population studied, and constituted chromosomal disorders occured in couples seeking IVF and ICSI with prevalence of 22.2% (8/38 couples), especially minor mosaicism of sex chromosomes in the female partners. The prevalence of chromosome abnormalities in infertile men was 17.7% (28/158), and in subfertile females, it was 26.4% (28/106).
 CONCLUSIONS: These results could indicate an increased tendency to miotic sex chromosome non‐disjuction in humans.

Down-regulated expression of perforin-positive/CD16+ cells in the peripheral blood lymphocytes in the first trimester of pregnancy and up-regulation at the end of pregnancy.

PROBLEM: Immunophenotypic profiles of perforin (P)‐positive peripheral blood lymphocytes in the first trimester and at the term of human pregnancy were analyzed.

Quantitative Analysis of Constitutive Heterochromatin in Couples with Fetal Wastage

PROBLEM: Heteromorphism of constitutive heterochromatin is a stable evolutionary feature that is thought to cause no phenotypic alterations. Nevertheless, the role of constitutive heterochromatin is still unknown. The instability of constitutive heterochromatin was generally restricted to T‐lymphocytes and was associated with variable immunodeficiency. The heterochromatin regions of chromosomes 1, 9, 16, and Y have been postulated to play a role in the immune response and during early embryo development.

Nonsurgical female sterilization: comparison of intrauterine application of quinacrine alone or in combination with ibuprofen

This study compares the results of nonsurgical female sterilization with quinacrine hydrochloride pellets alone or in combination with ibuprofen. From February 12 1988 to September 9 1992 150 women (group 1) aged 35 years or older underwent intrauterine application of quinacrine hydrochloride. 7 pellets of 36 mg were administered using a modified copper T IUD inserted during the early proliferative phase of two consecutive menstrual cycles. From September 11 1992 to May 14 1998 the same protocol was used in 222 women (group 2) of similar age except that 3 pellets each containing 18.5 mg of ibuprofen were added. After intrauterine application of the drugs the women lay supine with the pelvis elevated for 2 hours and were advised to use additional contraception (condom plus 5% nonoxynol-9 vaginal cream) between the first and second applications and for 2 months after the second application. The cumulative pregnancy rate after these methods of sterilization was calculated using the life table method. Overall results indicate that the 2-year and 5-year cumulative pregnancy rate signify the failure of ibuprofen to show any beneficial effects on the efficacy of quinacrine sterilization. Moreover age is a key determinant of the pregnancy rate after quinacrine sterilization. From the findings nonsurgical female sterilization such as intrauterine application of quinacrine pellets is generally less successful than surgical methods in prevention of pregnancy. Therefore attempts to improve its effectiveness should be considered.