Jan Friberg

Reproductive failure because of autoantibodies: Unexplained infertility and pregnancy wastage

Abnormal polyclonal B cell activation has been demonstrated in patients with endometriosis. To determine whether the noted B cell abnormalities were primarily a feature of the disease endometriosis or its manifestations of infertility and pregnancy wastage, we investigated antibody profiles in 26 female patients with unexplained infertility (group A) and 24 patients with unexplained pregnancy wastage (group B) but without documented endometriosis. Group A and B patients exhibited an unusual incidence of gammopathies (10 of 26 patients in group A and 11 of 24 in group B), with a majority representing immunoglobulin M gammopathies. Mean immunoglobulin M values were significantly elevated in both groups (p

The effect of endometriosis, its stage and activity, and of autoantibodies on in vitro fertilization and embryo transfer success rates*

OBJECTIVES To analyze IVF cycle parameters, including pregnancy rates (PR), in women with and without endometriosis and to evaluate the effect of the stage and activity of endometriosis and of autoantibodies. DESIGN A retrospective analysis of 237 consecutive IVF cycles (193 patients), 119 in women with and 118 without endometriosis. The endometriosis group was further subdivided according to the stage and activity of the disease and autoantibody positivity. SETTING Hospital-based and freestanding IVF programs with the same IVF team. PATIENTS One hundred ninety-three women of reproductive age undergoing IVF; 84 had prior diagnosis of endometriosis, and 109 had other indications for IVF. Within the endometriosis group, 40 did and 44 did not have evidence of active disease. Autoantibodies were measured in 50 patients. INTERVENTIONS The IVF protocol was standard with GnRH agonist administered from the midluteal phase of the preceding cycle. Variables included the method of ET and the use of corticosteroids. MAIN OUTCOME MEASURES Number of follicles produced, number of eggs retrieved, fertilization rates, number of embryos transferred, and PR per transfer. RESULTS There was no difference between groups in the response to stimulation, number of oocytes retrieved, number fertilized, and number cleaved. The overall PR was 27% per transfer; it was similar in women with and without endometriosis (29% and 25%, respectively). There was also no difference in PR according to the stage or activity of the disease. However, PR in autoantibody-positive and -negative patients were significantly different (22.9% and 45.7%, respectively). Among autoantibody-positive patients treated with corticosteroids, 8 of 10 conceived. CONCLUSIONS This study confirms previous reports that IVF success rates are comparable in women with and without endometriosis regardless of the activity and stage of the disease. However, our study also indicates that autoantibodies may affect adversely implantation of embryos and that this effect can be overcome by administration of corticosteroids.

The predictive value of hCG β subunit levels in pregnancies achieved by in vitro fertilization and embryo transfer: an international collaborative study

Serial human chorionic gonadotropin (hCG) beta subunit measurements of 300 pregnancies achieved by in vitro fertilization (IVF) were obtained by 15 IVF centers worldwide. Hormonal curves were established for 164 normal singleton pregnancies, 25 normal multiple gestations, 60 chemical pregnancies, 41 first-trimester spontaneous abortions, and 10 ectopic pregnancies. In comparison to the normal singleton pregnancy curve, chemical pregnancies and spontaneous abortions showed statistically lower hCG levels. hCG levels of ectopic pregnancies, compared with normal singleton gestations, were lower from days 7 to 14. It is concluded that beta-hCG determinations of in vitro fertilized pregnancies allow pregnancy diagnosis as early as 7 to 9 days after embryo transfer (ET) and will permit early discrimination between normal and abnormal IVF pregnancies. A single beta-hCG determination on day 9 after ET may discriminate chemical, ectopic pregnancy or impending miscarriage from a normal gestation. An hCG determination on day 17 will predict early normal development of an IVF pregnancy.

Intrauterine inseminations with washed human spermatozoa

The success of intrauterine inseminations with washed human spermatozoa was evaluated in four groups of patients. The first two groups were couples in whom either the man or the woman had detectable circulating sperm-agglutinating antibodies. The third group included couples where the woman exhibited hostile or absent cervical mucus, whereas the fourth group represented couples with oligozoospermic males. The couples underwent 3.7 +/- 2.1 insemination cycles, with a 30% overall pregnancy rate for all four groups. Intrauterine inseminations of women with hostile cervical mucus yielded a 68% conception rate. Couples with either male or female serum sperm-agglutinating antibodies showed 25% and 40% pregnancy rates, respectively. However, none of the couples with oligozoospermic males achieved pregnancy. Intrauterine inseminations with washed human spermatozoa thus represent a satisfactory method of achieving pregnancy in women with hostile cervical mucus and in couples with circulating sperm agglutinating antibodies. Couples in whom oligozoospermia has been identified as the principal cause of infertility do not seem to benefit from this therapy.

On the causation of pelvic inflammatory disease

The classic descriptive model of pelvic inflammatory disease (PID) omits any direct statement that sexual intercourse leads to the development of the lower genital or cervical infection which ultimately leads to upper genital or tubal infection. Despite this, clinicians treating patients with PID frequently, either implicity or explicitly, link its onset to sexual activity. In the past decade numerous authors have commented on the strong association between the widespread changes in sexual attitudes and behavior (without describing them in detail) and the enormous rise in sexually transmitted diseases and PID. With the advent of the case control study, the epidemiologist viewed sexual activity as only 1 of many risk factors for the development of PID. Yet, the clinician often maintanied that this relationship was too obvious to require case control studies to prove the point. The sum, the classic hypothesis on the pathogenesis of PID has remained virtually unchanged for nearly 8 decades in spite of its limitations, such as the failure to consider the endogenous and exogenous risk factors for the development of PID in a given patient. Possibly the greatest defect of the classic theory is its failure to address the precise mechanisms by which the infectious agents that cause PID travel from the lower to the upper genital tract. Existing literature suggests that 3 mechanisms may be operative. The 1st mechanism is that motile trichomonads are capable of ascending from the vagina to the level of the fallopian tubes and may carry with them a variety of infectious agents. The 2nd suspected mechanism for transport of microorganisms to the fallopian tubes is by attachment to sperm. If this occurs, then clearly spermatozoa may serve as vectors of pelvic infection. Abundant evidence exists to support the concept that sperm intimately associate with a variety of infectious agents, many of which are unrecognized as pathogens in the female. The 3rd suspected mechanism for transport of bacteria from the lower to the upper genital tract in the female appears to be that of passive transport. The literalture lacks reference to bacteria per se gaining entrance to the uterus but contains abundant references to the transport of particular matter and sperm. The current orientation of most American textbooks and much of the literature in regard to the pathogenesis of PID is oversimplified. More attention must be devoted to the mechanisms by which infectious agents arrive at the fallopian tubes.

Transcervical balloon tuboplasty.

TBT is a new technique that by use of a balloon catheter technique in a fashion similar to that of balloon angioplasty allows reestablishment of tubal patency in selected cases of tubal occlusion. The case presented here describes the first transcervical dilatation and recanalization of a proximally occluded fallopian tube in a patient with infertility.

Mycoplasma and human reproductive failure: III. Pregnancies in “infertile” couples treated with doxycycline for T-mycoplasmas

Abstract A total of 54 infertile couples from whom T-mycoplasmas were isolated were treated with doxycycline. Sperm-agglutinating antibodies were demonstrated in the sera from the female partners in 16 couples (Group A) and in 38 couples (Group B) no such antibodies could be demonstrated in either the male or the female. After eradication of T-mycoplasmas pregnancy occurred in 25 (Group A) and 29 (Group B) per cent of the couples. The possible significance of these findings is discussed.

Inseminations of human sperm after freezing in liquid nitrogen vapors with glycerol or glycerol--egg-yolk--citrate as protective media.

Ninety-three inseminations were performed with frozen human semen with the use of glycerol as a protective medium and 94 inseminations with glycerol-egg-yolkcitrate (GEYC) as a protective medium for the spermatozoa during freezing in liquid nitrogen vapors. During an 18 month period 10 pregnancies were obtained after inseminations with glycerol-treated semen and 16 pregnancies following inseminations with GEYC-treated semen.

Preliminary experience with transcervical balloon tuboplasty

We developed a new technique, transcervical balloon tuboplasty, an adaptation of established balloon angioplasty techniques that facilitates recanalization of proximally occluded oviducts. Sixteen patients with obstruction of the proximal portion of one or two fallopian tubes (based on at least two hysterosalpingograms and one laparoscopic examination) were selected for the procedure. Four patients (25%) were found to have patent oviducts on intraoperative third tubal patency evaluation and were therefore excluded from study. Of the remaining 12 patients; tubal patency was achieved in at least one fallopian tube in 7 patients (58%), as demonstrated by hysterosalpingogram immediately after the transcervical balloon tuboplasty procedure. On follow-up 2 months to 1 year afterward, two pregnancies and one delivery occurred. We conclude that transcervical balloon tuboplasty appears to represent a useful and safe technique to achieve patency in selected cases of tubal interstitial obstruction. Reocclusion rates, long-term complication rates, and pregnancy rates after transcervical balloon tuboplasty remain to be established before the procedure should be considered a recommended alternative for either surgical tuboplasty or in vitro fertilization.

Autoantibodies and common idiotypes in men and women with sperm antibodies

Antisperm antibodies have been implicated as a causative factor of infertility and pregnancy wastage. Since concomitant autoimmune phenomena were reported in men with antisperm antibodies, we investigated known antisperm antibody-positive sera from 25 women, 27 men, and the respective seminal plasma samples. The investigated autoimmune panel included a search for antinuclear antibodies, autoantibodies (in IgG, IgM and IgA isotypes) to seven phospholipids (cardiolipin, phosphatidylserine, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid), to four histone subfractions (H1, H2A, H3, H4), and to four polynucleotides [ssDNA, dsDNA, poly(I), and poly(dT)], total immunoglobulin levels, and sperm antibody titers. The sera were also evaluated for the presence of a common anti-deoxyribonucleic acid antibody, and anticardiolipin antibody idiotypes. Levels of sperm antibody titers were significantly lower in women than in men. Both men and women with antisperm antibodies demonstrated elevated total IgG levels compared with those of normal control subjects. Only women showed elevated levels of total IgM. Sera from 24% of women and 11% of men with antisperm antibodies demonstrated antinuclear antibody titers greater than 1:40. The most striking autoantibody abnormalities were found among antiphospholipid antibodies. Sera from women with antisperm antibodies demonstrated higher autoantibody production than was found in their male counterparts. A significant correlation was found between antisperm antibodies and IgM anticardiolipin and IgA anti-phosphatidylinositol in women and between sperm antibodies and IgA phosphatidylserine antibodies in men. The presence of anticardiolipin and anti-deoxyribonucleic acid antibody idiotypes was significantly more frequent in women than in men. By means of discriminant analysis and variables selected by this mathematical model, the identification of 24 of 25 women and 26 of 27 men with antisperm antibodies was correctly predicted. These results suggest that women and men respond differently to sperm antigens. The apparent cross-reactivity between sperm antibodies and other autoantibodies, usually associated with autoimmune disease, suggests that a polyclonal B cell activation, similar to that seen in autoimmune diseases, occurs in patients with sperm antibodies.