Celso-Ramon Garcia

Fertility control with oral medication

Abstract As the outstanding findings resulting from this investigation, we may state the following:n 1. 1. Length of the Menstrual Cycle.—n 1.1. A. The ingestion of 10 mg. of norethynodrel, supplemented by varying amounts of estrogen, on a prescribed day 5 through day 24 regime, resulted in a normal distribution of lengths of menstrual cycles. 1.2. B. If this regime is altered by omission of medication, there may ensue either shortened menstrual cycles, caused presumably by withdrawal bleeding, or lengthened menstrual cycles, resulting from adequate maintenance of the endometrium despite intermittent lack of medication or from prolonging of the treatment by use after the twenty-fourth day of the tablets missed earlier. 2. 2. Ovulation.—n 2.1. A. Presumption of suppression of ovulation is strengthened by the fact that conception did not occur in any instance in which the medication schedule of day 5 through day 24 was followed faithfully. 2.2. B. Among those who omitted medication for 3 or more days, the low incidence of pregnancy was roughly proportional to the number of unused tablets. 3. 3. Endometrium.—n 3.1. A. This compound appeared to exert a prompt progestational effect on the endometrium which, after 5 to 7 days of medication, did not progress in terms of glandular response, but did advance with reference to the stromal reaction. 3.2. B. No pathological endometrial changes were observed in specimens taken at different times in the cycle and after varying periods of medication up to 10 months. The sequence of endometrial response to medication, as well as of regression following medication, was generally quite regular, and no distinction could be made between endometrium from short-term and that from long-term treated subjects. 4. 4. Steroid Excretion.— Studies of urinary excretion of steroids indicated a decrease in 17-hydroxycorticosteroids and, to a questionable extent, of 17-ketosteroids. This decline did not seem to vary with the number of medication cycles, nor did it appear to be accompanied by any discernible signs of adrenocortical hypofunction. 5. 5. Blood Studies.— No significant differences in hemoglobin level were noted during or after medication as compared with those of untreated women. The average bleeding time, however, both during and after medication, was found to be significantly shorter than in the controls, while the clotting time in the postmedication subjects was significantly less than in either the control or the medicated group. 6. 6. Side Effects.—n 6.1. A. The treated subjects reported certain untoward reactions, the incidence of which did not vary with 0.8 to 1.8 per cent estrogen supplementation of the 10 mg. dose of norethynodrel. 6.2. B. It had been calculated that, over an 18 cycle span of medication, troublesome symptoms would cause approximately 27 per cent of the subjects enrolled in the project to discontinue treatment. Actually, in the course of the study to date, only 18 per cent have ceased medication because of side effects. 6.3. C. The administration of a magnesium aluminum glycinate antacid has led to the reported disappearance of untoward reactions in 82 per cent of the subjects who took the antacid. 7. 7. Fertility Control.— In practice, several difficulties have been encountered in maintaining complete fertility control, so that there have occurred 19 pregnancies, 5 of which were in women who had omitted 3 to 17 tablets from the advised regimen, and 14 in individuals who had stopped medication because of “reactions” or carelessness. These 19 produced a pregnancy rate of 13 per 100 marriage years, which may be compared with an expected incidence of 67 pregnancies per 100 marriage years from Puerto Rican women of this age range not known to be practicing contraception; or an actual incidence of 63 per 100 marriage years among these women (some of whom had been using contraceptives) before entering on the study. We believe that our data demonstrate the action of a powerful agent for fertility control among the women utilizing it. Thus far, in the subjects of our study, it has clearly lowered the pregnancy rate. The fact that 14 women who had discontinued medication after 1 to 17 cycles became pregnant within 1 to 3 months thereafter suggests that the drug, as thus used, does not interfere with subsequent fertility.

Behavioral and emotional factors: comparisons of anovulatory infertile women with fertile and other infertile women *

This controlled study compared behavioral and emotional factors in a group of anovulatory infertile women requesting treatment to achieve pregnancy. The sample comprised 49 women with secondary amenorrhea or oligomenorrhea in the treatment group, 141 women in the fertile comparison group, and 104 women with diagnoses other than anovulation in an infertile comparison group. Scores on the Hopkins Symptom Checklist (HSCL-90), the Eysenck Personality Inventory, the Langner Screening Scale, a Mood Analog Scale, and the Minnesota Multiphasic Personality Inventory (MMPI) were in the normal range and did not differ significantly between the groups. On other measures, the treatment group rated itself significantly less potent than to partner, mother, or father and reported more inhibited sexual attitudes than the comparison groups. Conclusions were that neurotic personality structure or psychopathology were not significantly greater in the treatment group than in the comparison groups. Whether the lower self-esteem and inhibited sexual attitudes of the treatment group resulted from or preceded infertility could not be determined.

A comparison of endometrial histology with simultaneous plasma progesterone determinations in infertile women.

A retrospective analysis of 238 endometrial biopsies and simultaneous plasma progesterone determinations performed during the course of infertility evaluations is presented. The data suggest a high (93%) correlation between the two procedures for the detection of ovulation. Endometrial abnormalities were detected in 5% of the biopsies. Shortening of the cycle was noted in 36% of the patients, while only 3% demonstrated a longer cycle. Simultaneous measurement of plasma progesterone levels in association with the endometrial biopsy is believed to better document corpus luteum defects. One should be aware of the frequent occurrence of a shortened cycle on the basis of postbiopsy bleeding. Basal body temperature graphs should be utilized prior to biopsy in patients with a history of irregular menstrual cycles.

Postoperative intraperitoneal adhesions: a double-blind assessment of their prevention in the monkey.

The effect of combined antihistamine and corticosteroid therapy and the effect of dextran on recurrent intraperitoneal adhesion formation were evaluated in 43 monkeys all of which had been previously used for reproductive tract studies and hence were suffering from adhesion formation to some degree. In a double-blind manner the monkeys were randomly divided into 3 experimental groups. 1 group received saline injections before and after lysis surgery followed by introduction of saline solution in the peritoneum during surgery. Group 2 was treated with saline injections as Group 1 except that dextran solution was introduced into the peritoneal cavity. In Group 3 a combined dexamethasone/promethazine therapy was administered before during and after surgery. In all of these monkeys the degree of adhesion reformation after adhesion lysis surgery was essentially the same in all 3 groups. Rather careful surgical technique was vastly more important than use of corticosteroids or antihistamines as prophylactic measures.

Human hydrosalpinx. Histologic study and chemical composition of fluid.

Abstract A histologic study of 9 hydrosalpinges and chemical analysis of their fluid content were performed. In most of the cases the wall was fibrotic; the epithelial lining in the main was impaired although in scattered areas it appeared normal and probably well functioning. Electrolyte values were similar to those found in the serum of the patients. Proteins and bicarbonate values were very low. Correlation between these low values and the functional potential of the hydrosalpinx should be considered, since it may be related to the degree of tubal damage. These aspects are discussed and the potential use of chemical study of hydrosalpinx fluid is reviewed. Consideration is given for use of the findings in evaluating functional prognosis prior to tuboplasty.

Effects of Microsurgical Removal of the Rabbit Uterotubal Junction

25 mature New Zealand white rabbit does (weighing between 3500 and 4500 grams) were used in an investigation to determine whether resection of the uterotubal junction (UTJ) alters the postovulatory functional blocking mechanism which keeps newly fertilized ova in the oviduct from 72-96 hours. A unilateral resection of the UTJ was performed in each animal. 2 of the 25 rabbits died 1-3 days following the anastomosis. 2 other rabbits refused the male although isolated on 2 occasions for a period of 21 days. In these 2 rabbits laparotomy disclosed a paucity of follicles in either ovary; no corpora lutea or adhesions were found and the anastomosis was patent. 10 additional rabbits failed to have pregnancies in either side despite many corpora lutea present in their ovaries. Many adhesions had formed in these 10 animals immobilizing their oviducts. Dissection of these adhesions around the oviducts revealed that the fallopian tubes were not distended with accumulated fluid and the anastomosed area was patent. 11 of the rabbits were pregnant on both sides. 8 of these animals were in good condition. In 2 there were fine adhesions between omentum and bladder and between intestines. In all instances the oviducts and uterine horns were free and mobile. A good correlation between the number of corpora lutea and the number of implantations of the control side was found.

Behavioral and emotional factors and treatment responses in a study of anovulatory infertile women

In a controlled treatment study of 49 anovulatory infertile women, responses to clomiphene citrate (CC) and placebo treatments were compared and associations of behavioral and emotional factors with treatment responses were investigated. In the first treatment series, ovulation occurred in 20 of 24 women in the CC group and 8 of 22 women in the placebo group. Pregnancy was achieved by 11 women during CC treatment and 3 women during placebo treatment. Overall, 28 women completed the protocol and 21 withdrew. Those who achieved pregnancy (n = 14) did not differ significantly from the ovulation-only group (n = 22) on pretreatment measures of emotional, behavioral, and personality factors including the Hopkins Symptom Checklist (HSCL-90), Eysenck Personality Inventory, Langner Screening Scale, Mood Analog Scale, Social Adjustment Scale, Mooney Problem Checklist, and the Minnesota Multiphasic Personality Inventory (MMPI). Conclusions were that a placebo response was observed in both ovulation and pregnancy, but psychologic factors as measured in this sample were not associated with these treatment outcomes.

Preservation of the ovary: a reevaluation

The incidence of routine ovariectomy approximates 20% to 30% of all women at hysterectomy. The propriety of this practice is evaluated from three perspectives: the review of the longevity of ovarian hormonal function throughout life, the review of the low risk of subsequent disease in the retained ovary, and the review of epidemiologic considerations. Because oophorectomy and the loss of its steroid contribution has such a profound influence on many body functions, with the most devastating relation to osteoporosis, and because there are no meaningful data in the literature to support the value of routine oophorectomy, removal of ovaries should only be performed when the ovaries are diseased.

Sexual behavior and steroid levels among gynecologically mature premenopausal women

Twenty-seven gynecologically mature young women who participated in a 14-week study prospectively recorded daily sexual behavior and basal body temperature data. In addition, they supplied plasma three times during the last cycle of participation. Plasma was analyzed for estradiol (E2), testosterone (T), and progesterone (P) by radioimmunoassay. The levels of circulating sex steroid hormones during the luteal phase were examined in relation to measures of menstrual cycle length, sexual frequency, and coital total. The results indicated the following: (1) women who had weekly sex with men had higher levels of estrogen than women who did not; (2) total amount of coital behavior was not related to any of the hormones assayed; (3) neither T nor P were distinguished by the consistency of sexual behavior or by coital total; and (4) women with aberrant-length cycles tended to have lower levels of E2. Thus, E2 consistently showed relationships to sexual behavior and cycle length, whereas P and T did not.

Clinical considerations of oral hormonal control of human fertility.

A review of the development of oral contraceptive agents (OCAs) is given with a list of the currently available progestin-estrogen combinations. Menstrual cycle phenomena (breakthrough bleeding amenorrhea pregnancy) are described along with methods of administering the drugs. Side effects such as those seen in early pregnancy are often seen (15-35% of the patients) in early cycles. Women with previous vascular problems varicose veins and other thrombophlebitis-inducing problems should be carefully watched during OCA therapy. Liver function abnormalities should cause discretion in OCA use. A hypothalamic-pituitary effect vs. a direct ovarian inhibitory effect is discussed. Ovarian activity returns promptly upon cessation of OCA therapy and resulting pregnancies are normal. Uterine vaginal ovarian breast adrenal and thyroid effects are summarized. It is noted that there has been no direct evidence suggesting a carcinogenic potential of OCAs. It is concluded that estrogen-progestin combinations are effective reversible and safe ovulation inhibitors.