Edward E. Wallach

Varicocele and male fertility.

Over the past 25 years the association of varicocele with male subfertility has been repeatedly demonstrated and the beneficial effect of varicocele ligation in infertile men with oligoasthenospermia has been documented. Since the precise mechanisms by which a varicocele affects spermatogenesis are still unclear, the proper approach to the management of asymptomatic varicoceles is controversial.

Ovarian smooth muscle in the human being, rabbit, and cat: Histochemical and electron microscopic study☆

Abstract The nature and distribution of smooth muscle cells in the ovaries of the cat, rabbit, and human being were investigated by both histochemical and electron microscopic studies. In the human ovary, the typical smooth muscle cells are abundant in both the theca externa of the follicle and the cortical stroma. In the rabbit ovary, smooth muscle cells are concentrated in the cortical stroma rather than in the follicle wall. In the cat ovary, the smooth muscle cells cannot be considered typical. The characteristic features of these cells are discussed, and the possible role of ovarian smooth muscle in the ovulatory mechanism is suggested.

Investigation of mammalian ovulation with an in vitro perfused rabbit ovary preparation

An in vitro perfused rabbit ovary preparation has been developed to study local factors responsible for the ovulatory process. This preparation enables: (1) isolation of the ovary from systemic influences, (2) direct serial observations of follicle development and ovulation, (3) addition to the perfusing medium of substances that may influence ovulation acting at the level of the ovary, and (4) correlation of the times of individual follicle rupture with ovarian contractile patterns. With this model the temporal requirements for human chorionic gonadotropin in the process of ovulation have been studied. The direct effects on ovulation of prostaglandin F3 alpha (PGF 2 alpha), the antihistamine chlorpheniramine, and calcium deprivation were also investigated. Chlorpheniramine and EDTA each led to inhibition of ovulation and depressed ovarian contractility. The use of the isolated in vitro ovary preparation permits characterization of the local requirements for ovulation.

Lysis of Periadnexal Adhesions for Correction of Infertility

A series of patients is presented in whom lysis of periadnexal adhesions was carried out for correction of infertility. These 35 couples had been infertile for at least 1 year prior to surgery. Seventy-seven per cent had been trying to conceive for more than 18 months. Following diagnostic evaluation, periadnexal adhesions were found to be the sole cause of infertility in 83% of cases. Subsequent to surgery, 63% of the patients conceived, 82% within 18 months, and 57% gave birth to at least one viable child. There can be no doubt that periadnexal adhesions represent true pathology. Although often seemingly insignificant in character, at the macroscopic level, they appear to play a major role at the microscopic level in impairing ovum pickup by the fallopian tube. Gynecologists should recognize the importance of these structures as mediators of a condition of relative sterility. Thus, despite the demonstration of tubal patency, the function of the rather delicate fimbria may be compromised by periadnexal adhesions, conglutinations, and hydatids so that only a fraction of those eggs that leave the ovary at ovulation reach the interior of the fallopian tube.

Microvasculature of preovulatory follicles: Comparison of in situ and in vitro perfused rabbit ovaries following stimulation of ovulation

Perifollicular vasculature undergoes significant morphologic changes as ovulation approaches. These vascular changes were observed in in vitro perfused and in situ rabbit ovaries by means of scanning electron microscopy of microcorrosion casts. Casts were made in in situ unstimulated ovaries, in situ ovaries stimulated with human chorionic gonadotropin, in vitro perfused unstimulated ovaries, and in vitro perfused ovaries after an ovulation-inducing dose of human chorionic gonadotropin, prostaglandin F2 alpha, histamine, or norepinephrine. Dilated vessels, extravasation of resin from weakened vessels, and filling defects at the apex of the follicle were observed in in situ ovaries 9 to 12 hours after stimulation and in in vitro perfused ovaries 4 to 6 hours after human chorionic gonadotropin. In vitro perfused ovaries stimulated with prostaglandin F2 alpha or histamine demonstrated dilated capillaries with extravasation of the resin and filling defects at the apex of large follicles. Norepinephrine-stimulated ovaries showed incomplete filling of vessels, although some large follicles showed extravasation of resin. The occurrence of dilated vessels, extravasation of resin, and filling defects is indicative of preovulatory vascular changes in both in situ and in vitro perfused ovaries, regardless of the ovulatory stimulus.

Oral contraceptives and neoplasia

n Some of the available data concerning the suspected association between oral contraceptive (OC) use and the development of cancer is surveyed, and the attempt is made to evaluate possible associations between OCs and human neoplasia in light of pregnancy risk or benefit of oral contraception. The principal investigative methods in humans include various epidemiologic approaches, and the methodologies most often used are case reports (tumor registries), disease rates and trends, case-control studies, and cohort studies. These methods cannot prove a causal relationship between exposure to a possible carcinogen and the occurrence of disease. Consistent positive or negative evidence, confirmed by multiple epidemiologic approaches, can be used to guide physicians and regulatory agencies in formulating policy for the clinical use of OCs. Both the progestogen-only and the combined OCs have been shown to have a protective effect on the development of benign breast disease with this protective effect not appearing until 2 years of use. Long-term combined OC use appears to be related to the development of benign liver neoplasia, and this risk increases with the dose of the steroid and the age of the user. These lesions are quite rare but may be life threatening because of potential spontaneous rupture and hemorrhage. Long-term postmenopausal use of estrogens appears to increase significantly the risk of developing endometrial hyperplasia and adenocarcinoma of the endometrium. Estrogens appear to be related to the growth of pre-existing uterine leiomyomas. Endocervical cells under the influence of progestogens may develop adenomatous changes, and these benign changes have on occasion been misinterpreted as carcinoma.n

Complications of female sterilization: immediate and delayed

Surgical sterilization in women has changed dramatically over the past 20 years. The development of laparoscopy and minilaparotomy have made the procedure readily available even in developing countries. In the United States, changing social values and changes in hospital regulations have done as much as technology to account for the tremendous increases in the number of women undergoing sterilization. Improved sterilization procedures have resulted in lower costs for sterilization and lowered morbidity and mortality rates. Hysterectomy for sterilization alone carries unacceptable morbidity and mortality rates. Originally, laparoscopic techniques utilized unipolar cautery. However, bowel burns, a rare but serious complication, were reported, and this led to newer techniques. These techniques, using bands, clips, and bipolar cautery, have gained increasing popularity and have eliminated many of the serious complications of female sterilization. Historically, there has been concern that tubal sterilization by any method produces, in significant numbers of patients, the subsequent gynecologic and psychologic problems called post-tubal ligation syndrome. A review of earlier literature indicates that many of these studies have serious methodologic problems, including recall bias, inappropriate control groups, failure to elicit prior history of gynecologic or psychologic problems, and failure to account for the use of oral contraceptives or IUDs. More recent large prospective epidemiologic studies that have controlled for prior gynecologic problems and contraceptive usage have failed to show increased incidence of gynecologic sequelae in large numbers of women. However, there are some data to support the concept that in certain individuals, sterilization may result in disruption of ovarian blood or nerve supply, producing gynecologic sequelae. Additional data from these ongoing large-scale studies and others should help to elucidate this problem in the future. Pregnancy after sterilization (even excluding pregnancies present at the time of the procedure) is more common the first year after the procedure with the risk decreasing in subsequent years.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Approach to the Evaluation of Sperm-Cervical Mucus Interactions *

A clinical approach to the evaluation of sperm-cervical mucus interactions is reviewed. The topics reviewed are 1) sperm passage through the cervix (sperm motility cervical mucus) 2) the cervical passage and infertility (the Sims-Huhner postcoital test the fractional postcoital test and intrauterine lavage in vitro systems the slide test the capillary penetrability test) 3) cervical mucus evaluation 4) sperm evaluation 5) management of cervical factor infertility and 6) prognosis.

Local ovarian effects of catecholamines on human chorionic gonadotropin-induced ovulation in the rabbit.

Observations were made on the local effects of the adrenergic drugs norephinephrine (1 mcg per kg weight) dibenzyline (.25 mg/kg) isoproterenol (1 mcg/kg) and propranolol (.1 mcg/kg) on HCG (Human Chorioic Gonadotropin) induced ovulation in 91 rabbits. All the rabbits received 50 I.U. of HCG and were operated on in identical fashion. Control animals received 1 ml of normal saline and showed 10 hours after HCG administration a mean number of 11.6 follicles per rabbit. There were 6.7 hemorrhagic and 4.9 mature follicles respectively. The test animals were divided into 2 groups; one group received the adrenergic agents 10 hours after HCG administration via injection into the abdominal aorta. The mean number of total follicles per rabbit was 10.1 for norepinephrine 11.3 for dibenzyline 7.9 for iso-proterenol and 10 for propanolol. Hemorrhagic follicles per rabbit were: 6.7 for norepinephrine 3.0 for dibenzyline 7.9 for isoproterenol and 10 for propranolol. The mean number of mature follicles per rabbit were: 3.5 for norepinephrine 8.3 for dibenzyline 2.3 for isoproterenol and 4.6 for propranolol. In the 10-hour post-HCG group the norepinephrine-injected group showed no significant difference from controls in either the number of mature follicles or hemorrhagic follicles. The dibenzyline-injected group showed a significant increase in mature follicles decrease in hermorrhagic follicles and delay or inhibition of ovulation compared with the controls. Isoproterenol was associated with a significant decline in the mean number of mature follicles compared with controls and with propanolol-injected animals. Propanolol-injected rabbits showed no significant difference from controls in either mature or hemorrhagic follicles. The second test group had norepinephrine or dibenzyline injected 7 hours post-HCG and ovarian morphology was followed up to 10 hours. Norepinephrine produced no change in either mature or hemorrhagic follicles compared with controls. Dibenzyline was injected in two dosages 7 hours after HCG: .25 mg/kg and 1.0 mg/kg. Ovarian morphology was followed up to 60 hours after injection and showed an increase in the number of mature follicles and a decrease in the number of hemorrhagic follicles. It appeared to delay the time of ovulation. The effects of d ibenzyline appear to be more profound when it is administered closer to HCG administration. Systemic administration (via the marginal ear vein) of dibenzyline resulted in minimal effects. Alpha-adrenergic blockage by dibenzyline is postulated to interfere with follicular rupture by preventing functional intervention of smooth muscle fibers in the ovary.

Monitoring of Ovulation Induction

The plasma hormonal patterns of the normal menstrual cycle have been reviewed. A consistent cyclic pattern of plasma hormone levels is observed in LH, FSH, estrogens, and progestins in the menstrual cycle. Other plasma hormones, such as ACTH, growth hormone, TSH, and PRL, as well as androgens and corticosteroids, fluctuate throughout the menstrual cycle without any consistent pattern during the ovulatory cycle. FSH, LH, E2, E1, P, T, and A levels during the induced ovulatory cycle are presneted for comparison. In the gonadotropin-induced ovulatory cycle most hormones behave in a manner similar to that in the normal ovulatory cycle, except for FSH levels, which rise continuously throughout the follicular phase of the cycle. Following ovulation in the gonadotropin-induced cycle, T rises above normal levels. Early in the clomiphene-induced ovulatory cycle, unlike the normal cycle, LH is distinctly elevated. Levels of both LH and FSH in the rest of the cycle simulate those in the normal cycle. However, T and A levels rise from the very beginning of clomiphene therapy and continue to rise throughout the clomiphene-induced ovulatory cycle. Levels of E and P are higher than in the normal ovulatory cycle, but a similar pattern is preserved. Because of the potential dangers of gonadotropin therapy, monitoring by frequent examination and laboratory tests is required. E monitoring is mandatory to evaluate follicular maturation, to time hCG administration, and to minimize hyperstimulation. Cervical mucus is an unreliable parameter for monitoring gonadotropin therapy alone. In addition to cervical mucus, plasma or urinary E should be monitored regularly. Clomiphene therapy is less dangerous than gonadotropin therapy. Because of its lesser risk, monitoring is rarely performed during clomiphene use. An active monitoring approach has been described. While this approach may not necessarily improve the outcome of clomiphene therapy, it may hasten the process of selecting the appropriate dose. Although other ovulation-inducing agents are available, their use is rarely associated with serious medical complications, and monitoring would seem unnecessary.