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Reproductive EndocrinologyGonadotropin-Secreting AdenomaGonadotroph AdenomaTranssphenoidal Resection

Gonadotrophin-secreting pituitary tumour: report and review

M D Whitaker et al., 1985Clin Endocrinol (Oxf)

A 34-year-old male with a pituitary adenoma was investigated and demonstrated to have hypersecretion of both gonadotrophins in the basal state. Immunocytochemical staining and electron microscopic examination were positive for tumour cells secreting FSH and LH. Presenting symptoms included visual disturbances, loss of libido, impotence, cold intolerance, frontal headaches, change in skin pigmentation and excessive weight gain. The patient denied alteration in hair distribution, had no acral features, galactorrhoea or gynaecomastia. Surgical extirpation resulted in complete amelioration of his symptoms over a three year follow-up period. Basal and stimulated pituitary function testing results returned to normal post-operatively. A review of the literature documents six other cases of pituitary tumour secreting both LH and FSH in the basal state. More commonly, the pituitary adenoma secretes FSH only. The literature is reviewed with regard to both types of tumour.

Fertility AwarenessNatural Family Planning OverviewMethod ReliabilityCouples Education

Natural methods of family planning

Flynn AM, 1984Clin Obstet Gynaecol

Reliable indicators to detect the fertile and infertile phases in the menstrual cycle are now available, largely due to the intensive scientific research into fertility over the past decade. This means that couples who follow the rules of the different NFP methodologies have a highly effective means of birth control, without the introduction of hormones, chemicals or devices into the body. New scientific techniques can be expected within the next couple of years which will simplify the detection of the fertile phase and hopefully help to elucidate the grey area of the early fertile days, where most of the unplanned pregnancies occur. Fertility awareness by both partners is an important positive contribution to the whole sexual relationship and emphasizes that NFP is an educational delivery system rather than a technological one. The modification of sexual behaviour and the motivation of both partners for the successful use of NFP may initially present a problem to some couples. On the other hand, many partners find the discipline enhances their sexual relationship and dialogue. Whatever the motivation, today more and more couples are happier to be in autonomous control of their bodies and their fertility.

Fertility AwarenessMethodological RulesInstructor TrainingUser Error Reduction

Natural family planning (NFP)

Luh-Hardegg G, 1984Geburtshilfe Frauenheilkd

The author reviews and makes further recommendations for 3 points of the discussion in G. Freundl's pilot study of "Natural Family Planning (Symptothermal Method) and Objective Ovulation Indicators" published by Georg Thieme Verlag in Vlume 6, "Geburtshilfe und Frauenheilkunde," in 1984. It is suggested that the scientific basis of changes in methodological rules, such as the BT3 modified for the double control method in paragraph 3 of the discussion, must be reported Natural Family Planning (NFP) instructors in Bonn, West Germany, along with failure statistics whenever possible, to enable instructors to participate responsibly. In response to errors by users cited in paragraph 4 of the discussion, the reviewer asserts that adequate instructional materials (photos and slides) are available to acquaint the users with changes in cervical mucus and that personal guidance of a couple or small group should be carried out until detection of fertility signals is performed without difficulty and the couple has proved itself capable of abstaining for the required periods, the latter being the more difficult. The author further cautions that before shortening of the abstinence period can be promoted, instructors must be scientifically assured of the accuracy of the basal temperature -6 indicator. She emphasizes that user errors can be reduced with a shorter abstinence period, but that the couple demands reliable rules first and foremost. The author concludes with a call for closer cooperation between gynecologists and NFP instructors.

Reproductive EndocrinologyBreast Cancer RiskDeficiency and DiseaseHormonal Assessment

Increased androgenic activity and breast cancer risk in premenopausal women

Secreto G et al., 1984Cancer Res

Blood and urine specimens from 27 premenopausal breast cancer patients and 62 healthy controls have been compared with respect to concentration of testosterone and progesterone in blood and of testosterone and androstanediol in urine, measured in the luteal phase of the menstrual cycle. There was a strong positive association between the concentration of the two androgens, either in blood or urine, and breast cancer risk. A strong association was also observed with decreasing levels of progesterone. The association was statistically significant (p for trend less than 0.01) for each hormone; the rate ratios were 10.2 for serum testosterone (highest category), 5.6 for serum progesterone (lowest category), 8.4 for urinary testosterone (highest category), and 5.2 for androstanediol (highest category). The rate ratio for women presenting both high serum testosterone and low progesterone was 21.8 (4.1 to 116.1). Considering the exposure to at least one of three androgens at the highest level and low progesterone, the rate ratio was as high as 90.2 (8.2 to 989.7). This study provides evidence for the hypothesis that increased androgenic activity is an important risk indicator for breast cancer, particularly when associated with anovulation, as indicated by low serum progesterone level.

Fertility AwarenessEffectivenessPhysiological BasisAcceptability

The Billings method of family planning: an assessment

Betts K, 1984Stud Fam Plann

The Billings/ovulation method is a periodic abstinence method of regulating births based on the client's interpretation of changing patterns in secretions of cervical mucus monitored by external self-examination. It was developed in Australia and is now widely promoted overseas. This paper outlines the method's recent history and goes on to discuss its physiological basis, its use-effectiveness as measured in a number of major trials, and some evidence concerning its general acceptability and applicability in family planning programs.

Contraception/ComparisonCopper vs Hormonal IUDBleeding and AmenorrheaContraceptive Devices

Intrauterine contraception with copper and with levonorgestrel: a randomized study of the TCu 380Ag and levonorgestrel 20 mcg/day devices

Sivin I et al., 1984Contraception

First year results of a randomized study of 1509 users of the Copper T380Ag with a silver core or of an IUD releasing 20 mcg day of levonorgestrel are reported. The cumulative gross pregnancy rate for each device was 0.3 per 100 at one year, with more than 490 women having one year of use with each device. The levonorgestrel-releasing device was associated with significantly fewer bleeding days and significantly increased hemoglobin levels when compared with pre-admission values or the one year values observed among users of the TCu380Ag. Terminations attributable to amenorrhea were significantly more frequent among users of the levonorgestrel-releasing device. The TCu 380Ag was associated with increased frequency and severity of dysmenorrhea compared with pre-admission levels or with the steroid-releasing device. Hemoglobin levels were somewhat reduced among users of the TCu 380Ag device. Terminations attributable to pain were, however, not significantly different by device. Continuation rates at the end of the first year were not significantly different by device.

EndometriosisCorpus Luteum DysfunctionSpontaneous AbortionProstaglandin-Mediated Mechanisms

Endometriosis and corpus luteum function. Is there a relationship?

Pittaway DE et al., 1984J Reprod Med

More than 100 years after the first description of endometriosis, the pathophysiology of the disorder still remains an enigma. In addition to infertility, an increased frequency of clinically apparent spontaneous abortions (32% vs. 8-15% in the normal population and 19% in the infertile one) has been found in women with endometriosis and secondary infertility. Treatment of endometriosis with conservative surgery, danazol or both results in a frequency of spontaneous abortion within the range of the normal population's. Although the factors involved in the pathophysiology of endometriosis are probably multiple, abnormal corpus luteum function is a common mechanism that might explain both the infertility and the spontaneous abortions. Several studies suggested a relationship between endometriosis and corpus luteum function, which may be mediated by prostaglandins. However, not all the data have been supportive. We developed a hypothetical scheme (modified from Drake) that outlines possible mechanisms of endometriosis mediated by the adverse effects of increased prostaglandins. Further investigation of this scheme may provide new information about the pathophysiology of endometriosis.

Reproductive EndocrinologyFetal EffectsSafety in PregnancyTeratology

The effect of medroxyprogesterone acetate (Depo-Provera) on prenatal development in the baboon (Papio anubis): a preliminary study

Tarara R, 1984Teratology

Six female olive baboons (Papio cynocephalus anubis) were treated with a single dose of 150 mg of Depo-Provera i.m. at day 30 of pregnancy, approximately three times the human dose equivalent on a body weight basis. Fetectomies were performed at day 100 of gestation. The body weights and measurements of the five live fetuses were comparable to age-matched controls and no gross or histologic abnormalities were seen. The dead fetus was in an advanced state of decomposition. This preliminary study suggests that, at levels up to three times that used for human contraception, Depo-Provera does not appear to have any adverse effects on fetal development.

Fertility AwarenessContinuation and DiscontinuationDeveloping Country ProgramsEducator-Client Relationship

Natural family planning in Mauritius, Indian Ocean: utilization patterns and continuance predictors

Conner GL et al., 1984J Soc Serv Res

Factors associated with discontinuation from an island-wide natural family planning program in Mauritius were examined in 2 stratified random samples of 300 (1976) and 350 (1980) acceptors. The data were gathered through records, educator observations, and field interviews with the 1980 sample. Comparison between those served by the Action Familiale program and characteristics of the Mauritius population as a whole suggests that the natural family planning program serves a somewhat better educated group of couples who have more employment security and smaller families than the general population. Acceptors selected the natural family planning method for reasons such as a desire to have a child according to a plan or to space children (29%), avoidance of the side effects of artificial contraception (21%), or as a result of a recommendation by a friend, relative, or professional (25%). 74% of acceptors in the 1980 sample expressed satisfaction with the method and indicated that their spouse shared this satisfaction. After 3.5-4.5 years of follow-up, 57% of acceptors in the 1976 sample had discontinued use of natural family planning. 9 variables in 4 categories--Administrative, Psychological-Motivational, Educator-Acceptor Relationship, and Family--were predictive of discontinuation. The major factors differentiating discontinuers 1) discontinuers had previously registered at Action Familiale and dropped out; 2) discontinuers placed more emphasis on spacing than on preventing pregnancies; 3) discontinuers discussed fewer topics with their educators; 4) discontinuers and their husbands seemed less interested in the natural method; 5) discontinuers had less family support for natural family planning; 6) educators experienced greater difficulty in teaching discontinuers; 7) discontinuers demonstrated less understanding of the symptothermal method; and 8) educators made fewer preregistration visits to the homes of discontinuers.

Research

Endometriosis and corpus luteum function. Is there a relationship?

Pittaway DE et al., 1984The Journal of reproductive medicine

More than 100 years after the first description of endometriosis, the pathophysiology of the disorder still remains an enigma. In addition to infertility, an increased frequency of clinically apparent spontaneous abortions (32% vs. 8-15% in the normal population and 19% in the infertile one) has been found in women with endometriosis and secondary infertility. Treatment of endometriosis with conservative surgery, danazol or both results in a frequency of spontaneous abortion within the range of the normal population's. Although the factors involved in the pathophysiology of endometriosis are probably multiple, abnormal corpus luteum function is a common mechanism that might explain both the infertility and the spontaneous abortions. Several studies suggested a relationship between endometriosis and corpus luteum function, which may be mediated by prostaglandins. However, not all the data have been supportive. We developed a hypothetical scheme (modified from Drake) that outlines possible mechanisms of endometriosis mediated by the adverse effects of increased prostaglandins. Further investigation of this scheme may provide new information about the pathophysiology of endometriosis.

InfertilityTamoxifenConception CyclesAnti-Estrogen Therapy

Endocrine profiles in tamoxifen-induced conception cycles

Tajima C, 1984Fertil Steril

Twenty-five infertile women conceived while taking tamoxifen (TMX). Daily serum profiles of 5 of the 25 TMX-induced conception cycles were elucidated and compared with those found in 5 normal cycles. In spite of lower levels of follicle-stimulating hormone and luteinizing hormone during the follicular phases, estradiol concentrations were higher in the TMX-induced conception cycles. It is suggested that this may be due to a direct ovarian effect of TMX as one of its major mechanisms in the course of folliculogenesis. On the other hand, progesterone concentrations on days 6 and 7 during the luteal phases were also higher in the TMX-induced conception cycles. It is suggested that this may be due to a luteotropic influence at the blastocyst stage.

PregnancyEtiology and Risk FactorsGenital InfectionsPreterm Delivery Prevention

Causes of preterm delivery

Gravett MG, 1984Semin Perinatol

Although major advances have been made in both obstetric care of the high-risk patient and in neonatal care, prematurity and its consequences remain the major contributor to perinatal mortality. The identification of maternal or obstetric risk factors associated with preterm delivery has enhanced our ability to provide special obstetric care to gravidas at increased risk. The selective management of patients at increased risk for preterm delivery may ultimately reduce the incidence of preterm births. Maternal genital infections are also associated with preterm delivery. Further research is needed to explore the pathogenesis of preterm delivery associated with genital infections, since infections may represent a potentially preventable cause of prematurity.

InfertilityTamoxifenAnti-Estrogen TherapyEstrogen Antagonists

Induction of ovulation with an estrogen antagonist, tamoxifen

Tsuiki A et al., 1984Tohoku J Exp Med

Tamoxifen (Norvadex), synthesized by the Imperial Chemical Industries Ltd., is a triphenylethylene derivative having a clomiphene-like structure and displays anti-estrogenic activities. In this study we used tamoxifen for the treatment of anovulatory infertility and investigated the clinical results. Induction rate of ovulation recorded 100% in the patients with sporadic anovulatory cycle, 83.3% in those with persistent anovulatory cycle, 70% in those with the first grade amenorrhea type I and 66.7% in those with the first grade amenorrhea type II. However, tamoxifen was absolutely ineffective against the second grade amenorrhea. The patients with sporadic or persistent anovulatory cycle responded to 40 mg-daily tamoxifen-treatment, recording 100% of ovulatory induction rate. The patients with the first grade amenorrhea also responded to 60 mg-daily treatment, indicating 70% of ovulatory induction rate. The rate of pregnancy established in the women desiring pregnancy marked 15.4%, and 2 out of 4 women with successful pregnancy experienced spontaneous abortion. Out of 4 patients who did not respond to the previous clomiphene treatment, 3 women accomplished ovulatory induction with tamoxifen. The endocrinological dynamics in the tamoxifen treatment were similar to those in the clomiphene treatment.

Reproductive EndocrinologyLH PulsatilityNeuroendocrine RegulationOpioid Modulation

Reduced frequency of pulsatile luteinizing hormone secretion in the luteal phase of the rhesus monkey. Involvement of endogenous opiates

Van Vugt DA et al., 1984Endocrinology

Pulsatile secretion of LH in women has been shown to vary during the menstrual cycle. LH pulse frequency during the luteal phase is markedly reduced compared to that in the follicular phase. The objectives of the present study were to determine if similar changes in pulsatile LH secretion occur in the monkey, and whether endogenous opiates are involved in producing these changes. In order to document if LH pulse frequency is reduced in the nonhuman primate luteal phase, serial blood samples were collected from 10 rhesus monkeys at 15-min intervals for 6 h at 3 different times of the luteal phase (early, mid-, and late). This pattern of secretion was contrasted to that observed during the ensuing early follicular phase. LH pulse frequency during the luteal phase was significantly reduced compared to the early follicular phase. Mean pulse frequency (+/- SE) was 0.84 +/- 0.16 pulses/6 h in the luteal phase vs. 2.99 +/- 0.58 pulses/6 h in the early follicular phase. When endogenous opioid activity was blocked during the luteal phase by a 5-h continuous infusion of naloxone (2 mg/h), an opiate antagonist, LH pulse frequency was increased to 2.48 +/- 0.25 pulses/5 h. This frequency was markedly different from the frequency of 0.85 +/- 0.17 pulses/5 h observed in the control period which immediately preceeded the naloxone infusion. The mean amplitude of the LH pulses in the luteal phase, which was significantly greater than that observed in the early follicular phase (20.9 +/- 1.9 ng/ml and 11.7 +/- 0.3 ng/ml) was not affected by naloxone (23.5 +/- 2.4 ng/ml vs. 25.3 +/- 1.9 ng/ml). Infusion of naloxone for longer periods (9 h) in 3 additional monkeys caused an increase in LH pulse frequency which was maintained in 2 of the monkeys, whereas the third animal exhibited only an acute response (a single pulse). These results indicate that the reduction in LH pulse frequency that occurs in the luteal phase of the rhesus menstrual cycle is an event in which endogenous opiates participate. Our previous finding that beta-endorphin release from neurons in the median eminence is stimulated during the luteal phase of the monkey, together with the present results, suggest that beta-endorphin functions as a modulator of pulsatile LH secretion in the primate menstrual cycle.

Fertility AwarenessUltrastructureScanning Electron MicroscopyCervical Mucus Changes

Preliminary results on the scanning electron microscopic structure of infertile human cervical mucus

Faccioli G, 1984Acta Eur Fertil

Interesting data on infertile human membranous mucus compared with infertile filamentous mucus have emerged from previous studies using scanning electron microscopy (SEM). The aim of this study was to obtain more information about the infertility of membranous mucus being independent of ovarian hormone stimulus. All different types of mucus, progressively secreted during the menstrual cycle by endocervical muciparous cells, were collected from the cervical canal of a fertile woman with a long menstrual cycle and specifically with a long infertile preovulatory period. The most significant results concern the identification of the cycle phase characterized by the presence of membranous mucus alone, i.e. the infertile preovulatory phase and the hormonal bases of membranous mucus infertility. The conclusion is reached that each ovarian hormone pattern stimulates the secretion of a specific type of mucus during the menstrual cycle.

InfertilityClomiphene Citrate Side EffectsHormonal InfluencesAnti-Estrogenic Effects

Antiestrogenic effect of clomiphene citrate: correlation with serum estradiol concentrations

Maxson WS et al., 1984Fertil Steril

The antiestrogenic effect of clomiphene citrate (CC) on cervical mucus was evaluated in women receiving 150 mg CC daily for 5 days. Daily cervical mucus scores and serum estradiol (E2) concentrations were determined in control (n = 25) and CC (n = 24) cycles. E2 concentrations were significantly higher in the CC-treated women (mean +/- standard error of the mean, 1254 +/- 102 pg/ml versus 337 +/- 18 pg/ml, P less than 0.0001). Despite supraphysiologic E2 concentrations, however, cervical mucus scores were significantly reduced in the CC-treated group (P less than 0.01). These data indicate that CC exerts a direct suppressive effect on cervical mucus despite markedly increased E2 concentrations.

Fertility AwarenessCanalization PhenomenonFerning and Channel FormationMonitoring Methods

Canalization of human cervical mucus

Garcea N et al., 1984Obstet Gynecol

Cervical mucus forms channels when dried under a coverslip. The 1) to prove mucus canalization both in spontaneous ovulatory cycles and during ovulation induction with gonadotropins; 2) to prove the estrogen dependence of this phenomenon; 3) to check the importance of the proteidic and electrolytic concentration on chaneling; and 4) to use this phenomenon clinically, shortening the time in which it occurs. The number and arrangement of channels vary during the cycle. The phenomenon is estrogen-dependent. The comparison between estradiol values and the number of channels during spontaneous ovulatory cycles and treatment with gonadotropins showed a linear relationship. Treatment with estradiol 17 beta-valerate and ethinyl estradiol induced channel formation in women with primary amenorrhea. Canalization and ferning disappeared after dialysis or treatment with proteolytic enzymes. It follows that the two phenomena have similar characteristics. Canalization increases daily, as does estradiol, whereas ferning maintains the same grade for a longer period, and when a grade of + + + is reached, it provides no further indications. With the use of a thermostat, canalization occurred in only a few hours. Chaneling, a more precise index, could therefore substitute for ferning, particularly when monitoring the induction of ovulation.

Reproductive EndocrinologyPharmacological SupportTamoxifen TreatmentAnti-Estrogen Luteotropic Effects

Luteotropic effects of tamoxifen in infertile women

Tajima C, 1984Fertil Steril

Tamoxifen at a dose of 10 mg/day for 5 days was given to five infertile women in the luteal phase. Daily serum samples were obtained during the luteal phase for radioimmunoassay of progesterone (P), estradiol (E2), follicle-stimulating hormone, luteinizing hormone (LH), and prolactin levels. The integrated luteal phase concentrations of serum P and E2 before and after cycles of tamoxifen treatment increased from 87.8 +/- 16.2 ng/ml and 1120 +/- 164.4 pg/ml to 131.6 +/- 18.9 ng/ml and 1461 +/- 205.2 pg/ml, respectively (P less than 0.01 and P less than 0.05). No apparent increase in circulating LH levels was seen in one of the five cases, but this patient's serum P and E2 levels rose nonetheless. This suggests that the significant increase in circulating P and E2 induced by tamoxifen is not consistently associated with an increase in serum LH concentration.

PregnancyCervical CerclageSurgical InterventionObstetric Interventions

A randomized controlled trial of cervical cerclage in women at high risk of spontaneous preterm delivery

Rush RW et al., 1984Br J Obstet Gynaecol

The effect of cervical suture on pregnancy outcome was studied in 194 women with a high risk (approximately 30%) of having a late abortion or a preterm delivery. The women were randomly allocated either to have a cervical suture inserted (n = 96) or to be managed without a suture (n = 98). There was no evidence that cervical cerclage either prolonged gestation or improved survival. Patients allocated to receive cerclage spent significantly longer in hospital, even when the period of admission for insertion was excluded. The patients in the cerclage group were more likely to receive tocolytic drugs, and more of them experienced puerperal pyrexia, although these differences between the groups were not statistically significant.

EndometriosisRetrograde MenstruationRetrograde FlowPeritoneal Fluid Findings

Retrograde menstruation in healthy women and in patients with endometriosis

Halme J et al., 1984Obstet Gynecol

Blood was found in the peritoneal fluid in 90% of women with patent tubes at laparoscopy during perimenstrual time. If the fallopian tubes were occluded, then only 15% of patients had evidence of blood in the pelvis. Also, 90% of patients with endometriosis and eight of nine women on oral contraceptives had bloody fluid during the menstrual period. The present observations indicate that retrograde menstruation through the fallopian tubes into the peritoneal cavity is a very common physiologic event in all menstruating women with patent tubes.

PregnancySubclinical ChorioamnionitisTocolysis FailureAmniotic Fluid Analysis

Silent chorioamnionitis as a cause of preterm labor refractory to tocolytic therapy

Hameed C et al., 1984Am J Obstet Gynecol

Thirty-seven consecutive patients with singleton pregnancies in "uncomplicated" preterm labor with intact membranes suitable for tocolysis were evaluated for evidence of silent chorioamnionitis by means of maternal serum C-reactive protein and amniotic fluid white blood cell count, Gram stain, and cultures. Abnormalities in these markers of infection were found to be significantly more common in cases that were refractory to tocolysis. These cases also showed both pathologic evidence of chorioamnionitis and a significantly greater neonatal early infectious morbidity. We conclude that silent chorioamnionitis is a significant cause of "uncomplicated" preterm labor refractory to conventional methods of tocolysis.

PregnancyCervical CerclageMulticenter StudiesCerclage Effectiveness

Multicentred controlled trial of cervical cerclage in women at moderate risk of preterm delivery

Lazar P et al., 1984Br J Obstet Gynaecol

A total of 506 women at moderate risk of preterm delivery were randomly allocated to either cervical cerclage or a control group. Significantly more women in the group allocated to cerclage were admitted to hospital for reasons other than the operation and more received oral tocolytic drugs. There were also more caesarean sections and more preterm deliveries in the women allocated to cerclage although the differences between the two groups were small and not statistically significant.

Menstrual CycleNormal VariationShort Luteal PhaseLuteal Phase Length

Normal variation in the length of the luteal phase of the menstrual cycle: identification of the short luteal phase

Lenton EA et al., 1984Br J Obstet Gynaecol

Normal probability plots were used to assess the homogeneity of a population of 327 luteal phases from apparently ovulatory menstrual cycles. The length of the luteal phase was defined as the interval (in days) following but not including, the luteinizing hormone peak, up to and including the day before onset of menstruation. A small sub-set of the population consisted of cycles with abnormally short luteal phases but the majority of the data followed a normal frequency distribution which gave a mean (+/- SD) for normal luteal phase length of 14.13 (+/- 1.41) days. It was estimated that all cycles with a luteal phase less than or equal to 9 days were abnormal, and that 74%, 22% and 2% respectively of cycles with luteal phases of 10, 11 and 12 days were also abnormal. The total incidence of short luteal phases defined as above was 5.2%.

DiagnosticsGlucose Testing AccessibilityDiabetes Self-Care

Use of tactile techniques for self-monitoring of blood glucose in visually impaired patients with diabetes mellitus

J C Prior et al., 1984Diabetes Care

Twenty-eight patients with type I diabetes mellitus, legally blind as a result of proliferative retinopathy, were recruited into a program designed to teach and evaluate tactile methods for self-monitoring of blood glucose (SMBG). Vision ranged from "blind" to "able to read large print." Techniques with wipe-off strips (Chemstrip bG or BM Test BG, Boehringer-Mannheim, Canada Ltd., Dorval, Quebec, Canada) use the opposite hand as a guide, operation of timing devices by touch, and special methods for labeling and storing strips. Methods with wash-off strips (Dextrostix, Ames Division, Miles Laboratories, Rexdale, Ontario, Canada) employ the fingers as a guide in directing the wash water. The accuracy of tactile methods was documented. Clinical parameters of glucose control improved in patients with adequate data after 6 mo of tactile SMBG. Glycosylated hemoglobin in 17 patients decreased from 11.3 +/- 2.1% to 9.4 +/- 1.5% (P = 0.005). Patients experienced significantly fewer reactions and low blood sugar readings as well as lowering of mean blood glucose values from 158 +/- 56 to 141 +/- 51 (P = 0.025).

Fertility AwarenessUse-EffectivenessDeveloping CountriesFertility Identification

Use-effectiveness of fertility awareness among the urban poor

Dorairaj K, 1984Soc Action

The efficacy, the ability of Indian women to use the Billings' Ovulation Method, and its effectiveness in helping them to control their fertility was studied in a sample of urban poor living in the Delhi slums. No attempt was made to develop a design which would rigorously test the acceptability of the method because the question of the ability of poor women to define fertility and to avoid an unwanted pregnancy by avoiding sexual relations during the fertility period; and the efficacy and use-effectiveness of the modified method which had not been tested. The study, which extended over 36 months, recruited a sample of 5752 eligible acceptors of fertility living in the urban slums. Natural family planning (NFP) use requires recurrent decision making at 2 in the beginning of the menstrual cycle to check for signs of fertility; and to abstain from sexual relations in the fertility period. Age was an important variable in the use of sexual abstinence oriented methods and fertility determining methods. 192 of the acceptors were below 19 years, 1545 between 20-24 years, 2089 between 25-29 years, 1236 between 30-34 years, 520 between 35-39 years, and 170 between 40-44 years. Of 4380 of the 5302 acceptors in Treatment 1 who began to use the method after menstruation, 7 (0.16%) had a profuse discharge and could not distinguish the change in mucus because of cervicitis which was treated in cycle 2. 663 (5.4%) acceptors did not see or feel fertile mucus but noticed patches of infertile mucus throughout the cycle. 419 (69.19%) of them had a family income of less than Rs300 and 25 (3.77%) were open cases of pulmonary tuberculosis. 16 acceptors (0.37%) noticed wetness and lubrication characteristic of fertile type mucus for about 2 hours, 145 (3.31%) for 3-4 hours, and 218 (4.98%) for nearly half a day. 867 (19.79%) had 1 day, 406 (9.27%) 1-1/2 days, 939 (21.44%) for 2 days, 291 (6.64%) 2-1/2 days, 636 (14.52%) for 3 days and 187 (4.27%) 3-1/2 to 4 days of fertile mucus. 1 acceptor had 5 days of fertile mucus. 4 acceptors failed to check regularly and therefore may have missed the fertile period. In Treatment 2 the initial decision to accept the use of the method was made by the 450 husbands before instructing their wives. The continuation rate of 91.86% for 12 months with a standard error of 0.67% was surprisingly high for a sample with low literacy and occupational status, low female work participation rates, small family size and a preference for sons with low motivation to use other methods. There were 9 unplanned pregnancies classified as method failures--pregnancies which occurred in acceptors who followed the method accoring to the instruction but got pregnant. The 1 year efficacy rate (life table analysis) was 99.86%. The 1-year use-effectiveness rate was 97.43% for the 5752 cohort. The high efficacy rate of the method can be due to 2 the correct identification of the fertile mucus; and the ability to clearly distinguish between infertile and fertile mucus.

Research

Luteinizing hormone receptor disorder in endometriosis

Rönnberg L et al., 1984Fertility and sterility

Luteinizing hormone (LH) receptor concentrations in ovarian follicles and corpora lutea were measured in 51 patients with histologically proven endometriosis and in 41 control patients. The LH receptor concentrations in cases of endometriosis were lower during the early (0.43 +/- 0.11 [mean +/- standard error] versus 1.31 +/- 0.27 fmol/mg protein; P less than 0.001) and late (0.48 +/- 0.10 versus 1.59 +/- 0.22 fmol/mg protein; P less than 0.001) follicular phase, and during the late luteal phase (2.62 +/- 0.55 versus 4.62 +/- 0.65 fmol/mg protein; P less than 0.05) of the cycle than in control patients. In contrast to the control patients, the LH receptor concentration during the follicular phase remained constant in endometriosis, being lower in patients with extensive or severe disease than in patients with moderate or mild disease (0.28 +/- 0.07 versus 0.61 +/- 0.21 fmol/mg protein; P less than 0.05). Endometriosis-associated infertility might be a consequence of a defect in the mechanism mediating LH action in the ovaries.

Research

Adolescent menstrual irregularity

Mansfield MJ et al., 1984Journal of Reproductive Medicine

Amenorrhea and oligomenorrhea in the adolescent female are often the result of anovulation due to an immature hypothalamic-pituitary-ovarian axis. A careful history, physical examination and selected laboratory tests can help to differentiate this type of transient menstrual irregularity from the large number of endocrine and anatomic abnormalities that also present in this age group. The HPO axis is not fully mature at menarche. Since the positive feedback response to estrogen, which allows ovulation, is frequently absent in the immediate postmenarchial period, menstrual 55% of cycles are anovulatory in the 1st year. With further maturation of the HPO axis a pattern of regular ovulatory cycles emerges. Basic evaluation is indicated if menarche does not occur by age 16 or if secondary sexual development does not begin by age 14. Secondary amenorrhea is the absence of menses for at least 3 months in a patient who previously had established cycles. Causes of amenorrhea in adolescents include pregnancy, drugs and systemic diseases, hypothalamic and pituitary amenorrhea, postpill amenorrhea, hyperprolactinemia, androgen resistance, congenital anomalies of the genital tract, and androgen excess.

EndometriosisSpontaneous AbortionMedical and Surgical TherapyRecurrent Pregnancy Loss

Endometriosis and spontaneous abortion

Groll M, 1984Fertil Steril

There seems to be an association of first-trimester spontaneous abortion and untreated endometriosis. In this report, 52% of an untreated group of patients with endometriosis aborted. However, 12% of a second group of surgically treated patients and 7% of a third group of patients treated with danazol aborted. Therefore, either medical or surgical therapy for endometriosis lowers the abortion rate significantly.

InfertilityClomiphene CitrateAdjunctive DexamethasoneDHEA-S and Ovulation

A randomized study of dexamethasone in ovulation induction with clomiphene citrate

Daly DC et al., 1984Fertil Steril

Improved understanding of follicular dynamics has led to a reevaluation of suppression of adrenal androgens in ovulation induction. To test whether adrenal suppression during clomiphene citrate (CC) therapy would improve ovulation/pregnancy rates, 64 anovulatory patients who had not previously received CC were randomly assigned to receive either 50 mg CC on days 5 to 9 alone or with 0.5 mg dexamethasone (CC + DEX). Patients were then screened for dehydroepiandrosterone sulfate (DHEA-S) (normal range, 80 to 320 micrograms/dl), prolactin, testosterone, and semen analysis of the partner. Nine patients discontinued participation prior to completing the first treatment cycle, and ten patients were found to have either elevated prolactin (4), severe male factors (3), or tubal disease (3) and were discontinued. CC was increased 50 mg/day per cycle through 150 mg/day until ovulation occurred. Once the patient was ovulatory on therapy, a properly timed postcoital test and endometrial biopsy for luteal phase defect were performed. If anovulatory at 150 mg/day of CC or demonstrating abnormal postcoital test or endometrial biopsy at 150 mg/day of CC, patients were crossed to the other arm of the treatment protocol. The results revealed a significantly higher rate of ovulation (P less than 0.01) and conception (P less than 0.05) in the CC + DEX-treated group. When correlated with DHEA-S levels, this improvement occurred in patients with DHEA-S greater than 200 micrograms/dl (P less than 0.05).

Reproductive EndocrinologyMenstrual Cycle

Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion

Filicori M et al., 1984J Clin Invest

The pattern of episodic gonadotropin release was studied in 15 normal female volunteers during the luteal phase of the menstrual cycle with 24 h of blood sampling for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at 10-min intervals. Six subjects (two in the early, two in the mid-, and two in the late luteal phase) also had each of these specimens processed for progesterone levels. A progressive slowing of LH pulsations was present across the luteal phase with the mean LH pulse frequency declining from 15.2 pulses/24 h in the early to 8.4/24 h in the late luteal phase. A trend towards reduction in the amplitude of LH pulses was also observed (12.3 +/- 2.2 SD mIU/ml in the early vs. 8.6 +/- 3.4 mIU/ml in the late luteal phase; NS). In addition, LH pulses of heterogeneous amplitude were identified during the same 24-h study. The mean +/- SD of the larger and of the smaller LH pulses was 16.9 +/- 4.7 and 2.3 +/- 1.0 mIU/ml, respectively (P less than 0.001). While the slowing of the frequency of all LH pulses correlated well (r = 0.80, P less than 0.001) with the day of the luteal phase and poorly with the actual plasma progesterone levels, the incidence of the small LH pulses was highest in the mid-luteal phase and correlated well with the mean progesterone plasma levels (r = 0.63, P less than 0.01). In the early luteal phase, the pattern of progesterone secretion was stable over the 24-h studies and showed no relationship to episodic LH release. In contrast, in the midand late luteal phase, plasma progesterone concentrations rapidly fluctuated during the 24-h studies from levels as low as 2.3 to peaks of 40.1 ng/ml, often within the course of minutes. Progesterone increments closely attended episodes of LH release, as documented by the significant (P less than 0.05) cross-correlation between LH and progesterone levels, at time lags of 25-55 min. The results of this study indicate (a) the frequency of pulsatile release of LH declines progressively and correlates well with the duration of exposure to progressively and correlates well with the duration of exposure to progesterone; (b) the amplitude of LH pulses varies with the appearance of an increased percentage of smaller pulses correlating well with the acute level of progesterone; (c) in the early luteal phase, the pattern of progesterone secretion is stable; (d) in the midand late luteal phase, progesterone secretion is episodic, and correlates with LH pulsatile release; and (e) single progesterone estimations in the midand late luteal phase do not accurately reflect corpus luteum adequacy.

InfertilityProgesterone TreatmentProgesterone SupplementationDiagnosis and Management

Outcome of progesterone treatment of luteal phase inadequacy

Wentz AC et al., 1984Fertil Steril

Diagnosis, choice of therapy, and pregnancy outcome were analyzed in 79 women evaluated for luteal phase inadequacy. Criteria for the diagnosis were established, and groups at risk for luteal inadequacy were identified. Treatment choices, tailored to the suspected cause, included progesterone suppositories in 54 women, with 23 pregnancies and 19 deliveries; clomiphene citrate in 6 women, with 2 pregnancies and deliveries; and combined treatment in 7 women, with 5 pregnancies and 4 deliveries. Eight women received no treatment, including three who underwent endometrial biopsy in the cycle of conception and who subsequently delivered. These data suggest that careful diagnosis and the proper choice of treatment are important, and that progesterone supplementation may result in improved pregnancy outcome for patients with infertility and pregnancy wastage who have luteal phase inadequacy.

SurgeryBarrier AgentsAnimal ModelsAdhesion Prevention

Adhesion prevention by solutions of sodium carboxymethylcellulose in the rat. I

Elkins TE et al., 1984Fertil Steril

Solutions of sodium carboxymethylcellulose (SCMC) were studied in rats to determine their longevity within the peritoneal cavity and their potential for prevention of postoperative intraperitoneal adhesions. In 18 rats, test solutions of SCMC and 10% dextran 40 were instilled at laparotomy. At 48 hours copious amounts of SCMC remained, whereas no 10% dextran 40 could be detected. In addition, standardized surgical injury was produced on the ceca of 100 rats at laparotomy. All control animals had significant adhesions at 2 weeks. Eighty-two percent of the 10% dextran 40 group had significant adhesions, while only 16% of the 0.9 wt% SCMC and 17% of the 1.0 wt% SCMC groups had significant adhesions. Solutions of SCMC were significantly more effective than 10% dextran 40 in the prevention of adhesions (P less than 0.001). Properties of SCMC and a possible mechanism for its striking effectiveness in adhesion prevention in this study are discussed.

InfertilityOocyte Release FailureFollicle Rupture DynamicsIVF Oocyte Recovery

Failure of human oocyte release at ovulation

Stanger JD et al., 1984Fertil Steril

Among 150 patients admitted for ovum aspiration, in vitro fertilization, and embryo transfer in Perth, Western Australia, 14 were found to have had at least one ovulated follicle at the time of laparoscopy. Based upon ultrasound estimation of follicle diameter 24 hours previously, ovulation occurred in 6 of 22 follicles less than 1.7 cm in mean diameter and in 16 of 19 follicles greater than 1.7 cm in mean diameter. When the ruptured follicles were flushed with heparinized fertilization medium, oocytes were collected in 13 of the 22 dispersed follicles. Twelve oocytes developed pronuclei 16 hours after the addition of spermatozoa, and 11 cleaved to the 4-cell stage within 44 hours of insemination. Oocytes were recovered from 6 of 11 patients stimulated with clomiphene alone and from all 3 patients stimulated with clomiphene supplemented with human menopausal gonadotropin. These observations suggest that oocyte release and follicle rupture are not necessarily synonymous events and that the incidence of retained oocytes in ovulated follicles following stimulation with clomiphene or clomiphene plus human menopausal gonadotropin could be on the order of 60%.

Ethics/PhilosophyDonor InseminationPatient Selection

The single woman and artificial insemination by donor

Strong C et al., 1984J Reprod Med

Requests by single women for artificial insemination by donor (AID) raise important ethical issues concerning the obligations of physicians and the well-being of the children who would be conceived. Specific objections to AID for single women can be raised, including that the absence of a father may adversely affect the child or that a lesbian mother may influence the child to become homosexual. A review of the relevant social science research indicates, however, that these and other objections are not supported by the available data. In support of AID for single women it can be argued that the life of the child who would be produced could be expected to have value, considered in itself. Consideration of the various aspects of the issue suggests that AID for single women is permissible in selected cases and that the physician has a right to refuse to carry out such requests.

Reproductive EndocrinologyIVF Luteal SupportLuteal Phase ManagementLuteal Phase Deficiency

Assessment and hormonal treatment of the luteal phase of in vitro fertilization cycles

Yovich JL et al., 1984Aust N Z J Obstet Gynaecol

Luteal phase lengths and hormonal profiles (progesterone, oestradiol-17 beta, beta HCG and prolactin) have been documented in 77 cases derived from a series of patients undergoing IVF. Nineteen pregnancies were generated during this series and 12 healthy infants have already been delivered. Luteal phase lengths were 14.5 +/- 0.5 days with 14.3% demonstrating mid-luteal progesterone levels of less than 31 nmols/l, considered to be low for successful conception. A random study of luteal support regimens comparing HCG or medroxyprogesterone acetate (MPA) with nil therapy was studied in a series of 44 consecutive embryo transfers during which 10 pregnancies were achieved. No difference was noted in the pregnancy rates for the 3 groups but the pregnancy outcome was better in those who had HCG support and this was more apparent in the overall series of 19 pregnancies. A significant luteotrophic effect was noted with HCG support regimens whilst MPA appeared to have a luteal suppressant action. Six pregnancies which aborted with blighted ova were derived from cycles in which the luteal phase progesterone levels were low raising the possibility that a poor hormonal environment may predispose to blighted ova.

Fertility AwarenessEffectivenessPatient EducationOvulation Detection

The ovulation method of family planning

Muzzerall L, 1984Can Fam Physician

With the Billings Ovulation Method of natural family planning, women chart the symptoms of changes of their cervical mucus to determine when they are ovulating. The Ovulation Method is simple to learn, and some studies have shown it to be 98.5% effective. It can be used throughout a woman's child-bearing years. Unlike other methods of natural family planning, a woman need not have regular menstrual cycles to use the Ovulation Method. Usually, volunteer married couples trained in the method teach it; however, the physician's support can greatly increase the competence of these instructors.

PregnancyPerinatal Psychiatric DisordersPostnatal DepressionAffective Disorders

Psychiatric disorder in pregnancy and the first postnatal year

Watson JP et al., 1984Br J Psychiatry

We interviewed 128 women regularly during pregnancy and the first postnatal year. Psychiatric interviews identified eight 'cases' of psychiatric disorder (6 per cent) in early pregnancy and twenty 'cases' (16 per cent) at six weeks after birth. Postnatal affective disorder, which accounted for 15 of these cases, was significantly associated with dissatisfaction with the marital relationship and also with previous psychiatric history. The implications of the term 'postnatal depression' are considered in terms of the course of the disorder in the 29 women (23 per cent) who had episodes of affective disorder at some time during pregnancy and the postnatal year. We found that the majority of episodes of affective disorder could be understood in terms of previous psychiatric history and/or reaction to life-events, including the stress of childbirth itself.

Reproductive EndocrinologyEctopic ProductionProlactin SynthesisProgesterone Effects

Prolactin production from proliferative phase leiomyoma

Daly DC et al., 1984Am J Obstet Gynecol

In vivo and in vitro endometrial stromal synthesis of prolactin occurs after progesterone-induced decidualization. Synthesis of prolactin by myometrium in vitro suggests that cells whose embryologic origin is the loose mesenchyme surrounding the paramesonephric ducts may retain the capacity to synthesize prolactin. Since physiologic myometrial synthesis of prolactin has not been demonstrated in vivo, prolactin genome expression in pathologic conditions was considered. Follicular phase leiomyomas were diced to 8 mm3 and cultured in Dulbecco's modified Eagle's medium (DMEM) with either no hormones, estradiol 200 pg/ml, progesterone 20 ng/ml, or estradiol and progesterone. Media were sampled and changed every other day for 8 days, followed by culture in tritium-labeled leucine DMEM for 2 days. Portions of leiomyomas were homogenized for initial prolactin content, and all samples were assayed for prolactin by radioimmunoassay. Follicular phase leiomyomas contained prolactin (47 +/- 15 ng/gm) in excess of normal serum values. Synthesis was demonstrated during all time periods from leiomyomas not exposed to progesterone. Progesterone variably suppressed the synthesis of prolactin until after 144 hours of culture. Determination of molecular weight on a 60 by 1.5 cm Sephadex G-100 column revealed identical estimates for pituitary, decidual, and leiomyoma prolactin. Tritium-labeled leucine incorporation into prolactin was confirmed by immunoprecipitation of Sephadex G-100 column fractions. Similar antigenicity was confirmed by parallel dilution curves for pituitary, decidual, and leiomyoma prolactin. Preliminary bioactivity in lymphoma proliferation assays confirmed prolactin activity. The conclusion reached was that proliferative phase leiomyomas contained elevated prolactin presumably secondary to in vivo synthesis. This synthesis was confirmed in vitro.

Menstrual CycleUltrastructural AnalysisCervical Mucus EffectsHormonal Correlates

Hormonal bases of the correspondence between microscopic and ultramicroscopic features of human cervical mucus

Faccioli G, 1984Acta Eur Fertil

By studying the changes of microscopic and ultramicroscopic structure of cervical mucus and the corresponding changes of ovarian hormone levels throughout the cycle, a close correspondence was found between micro and ultramicrostructures. The optical structure of non canalized mucus and the electronic features of membranous mucus maintained a similarly unvaried morphology in spite of the striking changes in hormonal levels during the cycle. On the contrary, a varied morphology corresponding to the changes of cyclic levels of ovarian hormones was observed in the optical structure of canalized mucus and in the electronic features of filamentous mucus. Therefore, whatever its micro or ultramicroscopic features, the dehydrated mucus showed two components, one dependent and the other independent of ovarian hormones. A similar conclusion has also been reached for fresh mucus components.

Fertility AwarenessProgram ImplementationDeveloping CountriesFamily Planning

Natural family planning in the Philippines

Laing JE, 1984Stud Fam Plann

The calendar rhythm method of natural family planning (NFP) is one of the most popular contraceptive methods in the Philippines. As a result, the Philippines has one of the highest NFP prevalence rates in the developing world. In recent years, family planning program officials have become increasingly interested in improving the practice of NFP, both by improving the quality of rhythm practice and by introducing newer, more accurate NFP methods. Over the years a substantial body of research data related to NFP practice in the Philippines has accumulated. This paper presents major findings from past research on NFP in the Philippines, discusses their implications for program management, describes current research, and suggests needs for future research.

Fertility AwarenessUser AttitudesPhilippinesFocus Groups

Attitudes toward the rhythm method in the Philippines

Verzosa CC et al., 1984Stud Fam Plann

Two sets of focus group discussions on the advantages and disadvantages of the rhythm method were carried out in the Philippines in 1980 and 1981. The first discussions were held among 30 women and nine men 21-40 years of age, and the second among eight women 25-35 years of age who had voluntary pregnancy terminations after the method had failed. Among the perceived advantages of rhythm were that it permits spontaneous intercourse on the safe days and has no bad side effects. Among the perceived disadvantages were that it is ineffective, especially for women with irregular periods, and it requires abstinence. The women who had had voluntary pregnancy terminations discussed their motivations and rationales and the methods that they had used. The information obtained from the discussions formed the basis for support materials that are now used throughout the country.