Acyclovir treatment of twelve unexplained infertile couples.

Because of recently published research showing herpes antibodies in the endometria of patients who had aborted, as well as evidence of subacute inflammation of the endometria, 17 couples suffering from long-standing totally unexplained infertility (except for persistent subacute inflammation of the endometrial were given acyclovir over a period of six menstrual cycles. Five of these couples did not complete the treatment protocol. Of the 12 couples who did, 5 became pregnant, with successful pregnancies. Two of the five had posttreatment endometrial biopsies that were negative, and both became pregnant subsequently. In contrast to their past histories, there were no spontaneous abortions.

Mycoplasma, chlamydia, Epstein-Barr, herpes I and II, and AIDS infections among 100 consecutive infertile female patients and husbands: diagnosis, treatment, and results.

One hundred consecutive infertile patients were studied to determine the incidence of sexually transmitted diseases (STDs) among middle and upper income patients, most of whom were referred as longstanding failures by other physicians. There were no cases of syphilis, gonorrhea, or AIDS found among these patients. One patient was pregnant when first seen, and was eliminated. Genital mycoplasmas were cultured from 64 wives. Antibodies for past or recent infection with Chlamydia were present in only 23. Antibodies to Epstein-Barr virus and to herpes II were found in 92 and 65, respectively. If only the mycoplasmas, Chlamydia, and herpes II are considered possible causes of human infertility, only 7 of the 99 couples showed no evidence of ever having had any of these three infections. Edometrial histology was positive for the changes associated with Mycoplasma infection in 47 of the 86 patients biopsied. Of the 39 with negative biopsies, 24 yielded positive cultures for Mycoplasma. Hence, only 15 of the 99 patients were negative for Mycoplasma by both culture and/or endometrial histology. Treatment with the antibiotic of choice, as indicated by sensitivity testing of all Mycoplasma-positive cultures, was an important factor in producing 43 pregnancies during the first year of study. Two of these were ectopic; 11 were spontaneous abortions, with one of these women now pregnant again and in mid-trimester; 28 have delivered healthy babies; and two are still pregnant and doing well.

Prognostic value of subacute focal inflammation of the endometrium, with special reference to pelvic adhesions as observed on laparoscopic examination. An eight-year review.

The significance of the endometrial lesion known as subacute focal inflammation (SFI) (or the more descriptive term lymphoid aggregates [LA]) as a factor in reproductive failure is controversial. We correlated the pelvic findings of 262 consecutive laparoscopic procedures performed for infertility with the histologic diagnosis from an endometrial biopsy that had been obtained previously as part of the infertility evaluations. Pelvic adhesions were observed in 87.3% of women in whom the diagnosis of SFI had been made. Pelvic adhesions were observed in only 10.9% of women whose biopsies did not contain SFI. Of women with SFI on biopsy but without pelvic adhesions, 70.6% demonstrated American Fertility Society stage I endometriosis at laparoscopy. These findings are statistically significant (P less than .0001).

Dysplasia of the lower genital tract in the female monkey, Macaca fascicularis, the crab-eating macaque from Southeast Asia.

Seventy-eight female reproductive tracts from mature Macaca fascicularis caught in the wild were examined histologically for evidence of dysplasia in immature (metaplastic) and native (mature) squamous epithelium of the cervix and vagina. This series contained equal numbers of experimental animals and control and/or breeding colony animals. Five of 39 experimental animals showed dysplasia, whereas six animals with definite and two with questionable dysplasia were found in 39 control and breeding colony animals. On the basis of the foregoing facts, it would appear that these dysplastic lesions were of spontaneous origin and of undetermined etiology. Therefore, those investigators who experiment upon the reproductive tract of this species of monkey should be wary of interpreting any given experiment as "causing" dysplasia. Monkeys of this same species, born and reared in our Primate Center, have been examined for comparable dysplastic lesions of the lower female genital tract. None was found thus far but the study is continuing.

Vaginal adenosis in Cebus apella Monkeys exposed to DES in utero.

Vaginal adenosis comparable to that seen in DES-exposed human newborns exposed to diethylstilbestrol (DES) was observed in 4 (100%) female Cebus apella monkey neonates exposed to DES in utero. Columnar Epithelium lined the vaginal canal and deep crypts in the underlying stroma. The ectocervix was markedly papillary and covered with columnar epithelium that was continuous with the endocervical epithelium. By comparison, the vagina of unexposed newborn and juvenile cebus monkeys up to 15 months of age was filled with a solid core of squamous cells that also covered the cervix and extended into the endocervix. Vaginal adenosis has been produced in mice by neonatal treatment with DES. The mouse model, however, excludes the fetoplacental unit. The cebus monkey provides a model for the investigation of teratogenic effects of intrauterine exposure to DES.

Vaginal adenosis in stillborns and neonates exposed to diethylstilbestrol and steroidal estrogens and progestins.

A histologic study was conducted of sagittal sections of the genital tracts of 281 autopsied female stillborns and neonates. The prevalence of vaginal adenosis among 43 offspring exposed in utero to diethylstilbestrol (DES) was 70%, a frequency 18 times greater than the 4% prevalence among 159 unexposed offspring. The relationship of the prevalence of vaginal adenosis to the gestational age at initial exposure was highly significant: 81% of those first exposed during the period of vaginogenesis had adenosis, whereas none exposed after 21 weeks' gestation had adenosis (P1 = 1 X 10(-4)). The relationship of the prevalence of vaginal adenosis to the total dose of DES prior to 22 weeks' gestation also was significant (P1 = 0.02), and this relationship was independent of gestational age at first exposure (P1 =0.01). In contrast, the prevalence of adenosis among 23 offspring exposed to steroidal estrogens and progestins was about the same as that among the unexposed offspring. Vaginal adenosis was unrelated to the complications of pregnancy for which the hormones were given, the calendar year of birth, and the gestational age at delivery.

The female genital tract of the owl monkey (Aotus trivirgatus) with special reference to the ovary.

The female reproduction tracts and ovaries of 30 owl monkeys, Aotus trivirgatus, were examined morphologically using the light and electron microscope. The animals ranged in age from a third trimester stillborn fetus to those of mature old age. The epithelia of the generative tracts were inactive or resting; evidence of prior menstruation was occasionally evident from hemosiderosis in endometrial stroma. Cyclicity of estral or menstrual type, however, was not established. One pregnant uterus (11-12 days gestation) was in the series. Prior pregnancy was deduced by the presence of perivascular fibrosis of myometrial vessels. The immature ovary contained an occasional developing or involving Graafian follicle, but no interstitial tissue. The mature ovary developed large, multilobulated masses of luteinized interstitial tissue which occupied the medulla, crowded the hilum, and thinned the cortex. Small dark intracortical cells, derived from cortical stroma, became foamy, lipoid-laden, contained hemofuscin, and formed the peripheral zone of the interstitial cell masses. The theca interna of involuting follicles appeared to be a significant source of the inner cells of the interstitial masses. Ultrastructure of the outer pigmented cells of luteal interstitial masses suggested steroidal activity; the function of the inner cells was not morphologically evident. Corpora lutea could not be identified with certainly, either by form, stigmata, or histology; nor could they be differentiated from interstitial masses. The latter appeared, therefore, to act in concert as a single, massive bilateral corpus luteum.

Ultrastructure of quiescent oocytes of Cebus albifrons.

Quiescent oocytes of the monkey Cebus albifrons were examined with the electron microscope. In many respects the ultrastructure of these cells was similar to that of other mammalian species. Elongate and oval mitochondria, lamellar Golgi complexes, small profiles of smooth endoplasmic reticulum, and vacuolar organelles were randomly distributed around a round nucleus which usually contained a nucleolus and clumps of heterochromatin. Among the unusual morphological characteristics of these oocytes are 'membranous aggregates', membrane-bound organelles containing a complex of convoluted membranes, some very dense rod-like structures and a droplet of moderate density which resembles lipid. A similar droplet is frequently found in mitochondria. Rough endoplasmic reticulum is abundant in many of these oocytes, forming parallel arrays and concentric rings around the nucleus. Folded membrane complexes, apparent elaborations of smooth endoplasmic reticulum, are frequently found in the cytoplasm in continuity with cisternae of smooth and rough endoplasmic reticulum and associated with vesicles which often contain flocculent material. The morphology of Cebus oocytes suggests a greater rate of steroid and protein synthesis, transport, and storage than is usually indicated by the ultrastructure of other mammalian oocytes.