Search

A prospective study of sex preselection provided the opportunity to characterize the fertile menstrual cycle. We describe from 91 natural conceptual cycles, or sub-groups thereof, cervical mucus symptoms, basal body temperature (BBT) changes, hormonal characteristics, and the outcome of pregnancy. The cervical mucus symptoms defined a potential fertile period of 10 days' average length, with the "peak" mucus symptom occurring at a mean of day 15.5 of the cycle. A fertile period of 9 to 10 days was also indicated by pregnancies resulting from single acts of intercourse between -6 and +3 days from ovulation. The BBT chart was biphasic in 73 of 76 cycles. The duration of the LH surge as observed in early morning urine samples averaged five days, with the peak occurring 1.4 days after the onset. Considerable inter-subject variability was seen in the LH excretion levels. Hormone measurements of peripheral plasma during the luteal phase showed the first detectable presence of hCG between day 7 and day 13 after conception. Progesterone concentrations in the midluteal phase exceeded 20 nmol/L and tended to be higher than in a comparison group of nonfertile cycles, whereas the estradiol concentrations were similar in fertile and nonfertile cycles. The birth sex ratio favored males when intercourse preceded ovulation/fertilization by two days or longer. While this association was statistically significant, the number of pregnancies involved is too small to conclude that the relationship is real.

Incubation of human spermatozoa in capacitation media for 24 hours resulted in a significant increase in acrosome-reacted spermatozoa compared with preincubation (baseline) levels. By contrast, sperm samples recovered from the cervix for as long as 72 hours after coitus showed only baseline percentages of acrosome-reacted spermatozoa. These results indicate that human spermatozoa do not undergo the acrosome reaction during cervical storage even if they undergo capacitation.

Ovulation disorder as a possible cause of a cervical factor problem was evaluated in 30 patients with poor postcoital tests. The diagnosis of an ovulatory defect was based on follicular maturation studies included in serial pelvic ultrasonography and serial assays of serum estradiol and progesterone. Patients were divided into three groups with cervical factor presumably due to (1) immature follicular development, (2) premature luteinization, and (3) pure cervical factor. A higher pregnancy rate was achieved in the group with pure cervical factor when the therapy was directed exclusively toward improving the cervical mucus. However, a significant improvement in pregnancy rate was observed when therapy was aimed at correcting both abnormal follicular maturation and the cervical mucus problem. Combined use of pelvic sonography and quantitation of serum estradiol and progesterone allow the clinician to select the treatment for cervical factor that is most likely to achieve successful pregnancy.

A study was designed to determine the incidence and etiology of the unexplained poor postcoital test. An in vivo comparison of sperm penetration by husband's versus donor sperm in the wife's estrogen-stimulated mucus was performed. The 8 of 30 women showing improvement of husband's penetration in mucus (group 1) were treated with high-dose estrogen (HDE) and hMG, and 4/8 conceived. Anti-sperm antibodies (ASA) were insignificant in this group. In group 2, in which donor sperm penetrated but husband's sperm did not, 8 men of 17 were found to have an ASA level over 50% on the sperm surface; 6/8 treated with high-dose methylprednisolone (MP) had an improved postcoital test, and 5 achieved a pregnancy. Two patients with levels under 50% were still treated with MP, and one achieved a pregnancy. In five group-3 couples, positive ASA were found in the cervical mucus of two women; and one woman improved on the postcoital test and conceived following MP therapy. The 30 unexplained poor postcoital tests occurred in 5,000 couples evaluated. In general, those patients considered to have significant clinical antibody had levels over 50%. Because side effects of MP may be severe, and positive ASA may be found in normal donors, it is important to use a comparison penetration test to help determine if treatment with corticosteroids seems reasonable.

The possibility of the immunological factor as an etiological cause of infertility was investigated in 50 infertile couples. Of these, 31 couples were considered as an "unexplained sterility" group, while in the other 19 couples a variety of disorders were diagnosed. In vitro, leucocyte migration inhibition test (LMIT) was used for the detection of female cell-mediated immunity against sperm antigens. Sperm immobilization test (SIT) and sperm toxicity tests (STT) were used for the detection of antisperm antibodies in the cervical mucus. Out of the 31 "unexplained sterility" cases, six revealed a positive LMIT (5.3%). In 26 couples with an abnormal postcoital test (PCT), 10 cases had a positive SIT and STT (38.5%). However, out of the group of 16 couples with a normal PCT only in one case was a positive SIT and STT found (6.2%). The potential role of immunological reactions in infertility will be discussed.

In a case of infertility due to cervical factor, application of donor mucus into the cervical canal was effective. The donor mucus with the first fraction of the husband's split ejaculate were incubated at 37 degrees C for 20 minutes. The mucus was then introduced into the cervical canal and a cervical cap for insemination was applied. A positive postcoital test was demonstrated after 6 hours. The patient conceived following a second such treatment. Donor cervical mucus aplication and insemination seem to be of value in the treatment of cervical factor.

Cervical mucus is an aqueous or gel mixture of fluids, ions and compounds, and cells, primarily produced by the endocervical epithelium. The amount secreted varies with menstrual phase and compositions changes under hormonal influence. Sodium shows the greatest concentration change at ovulation but does not change early enough to be of value in natural family planning practice. Dried mucus has a fern appearance due to NaCl crystals at ovulation. Other substances, less clearly related, are too difficult to analyze or in too low concentration. Soluble proteins, amino acids, and simple sugars show wide fluctuation and probably influence sperm penetration and nutrition. One function of mucus is antimicrobial activity of leukocytes, which decreases at midcycle. Another, sperm transport, is a function of estrogen's effect on mucus rather than ovulation. Sperm concentration in the mucus column is maximal from 15 minutes to 2 hours after vaginal deposition. Rapid penetration into cervical mucus favors sperm survival because of its optimal pH. Infertility may be caused by immunoglobulins or spermagglutinins in cervical mucus. To date, no constituent of cervical mucus has been identified which undergoes an easily detectable change 4 days before ovulation. Several potential methods for use in natural family planning are suggested.

The symptothermal methods include all those that identify the woman's fertile period through the basal body temperature and the periovulatory signs. Research conducted following the discovery over a century ago of the hyperthermic plateau in the later part of the menstrual cycle has confirmed that under normal conditions, and when the daily temperature is taken under comparable conditions, infertility may be assumed when the high temperature plateau is confirmed. A reliable temperature curve requires certain conditions: it should be taken upon awakening with a basal thermometer over a sufficient time to obtain an accurate measure, at almost the same time every day, and the graph paper should be appropriately scaled for recording. Various guidelines of interpretation have been developed throughout the world. Serena considers infertility assured from the 3rd consecutive day of elevated temperature as long as other fertility symptoms have disappeared. Among symptoms of ovulation that are perceptible to the woman are cyclic changes in the quantity and consistency of the cervical mucus, which has the advantage of predating and thus forecasting ovulation and of being less sensitive than the basal temperature to nongenital infections, sleepless nights, or other stresses. Use of mucus changes alone as an indicator of fertility carries the risk that such changes may not be noticed or may be due to an estrogen surge not related to ovulation. Other symptoms that are useful for some women in confirming temperature or mucus changes include 4 different alterations in the cervix, abdominal pain or mittelschmerz, intramenstrual bleeding, feeling of heaviness in the breasts, and variations in mood and libido. Many groups that teach the temperature curve and clyclical symptoms also provide instructions or mathematical rules for determining the number of infertile days at the beginning of the cycle. Some programs state that 6-7 days are usually infertile provided that the menses were preceded by a hyperthermic plateau. Many groups recommend the calculation of Ogino or a variant. The symptothermal method of fertility control combines the basal temperature curve with the other signs of fertility to serve as a basis for modification of sexual behavior to enhance or suppress fertility. Different programs stress different elements or combinations. The efficacy of the symptothermal methods depends on precise recordkeeping and observation and on competent instruction and counseling, as well as the willingness of the couple to modify their sexual behavior. Statistical measures of the method's efficacy are complex and unsatisfactory as they attempt to apply rigid rules to actions and decisions that are in fact filled with nuance.

We have studied the principal chemophysical properties of cervical mucus obtained before and after diathermocoagulation (DTC) in 35 patients participating in a program for prevention of cervical carcinoma. Two months after DTC there were significant decreases in the cervical scores for both exo- and endo-cervical mucus (Moghissi scale). Twelve patients with favorable pre-DTC scores, whose condition had deteriorated 2 months subsequent to treatment, again displayed normal scores in both sites 1 year after DTC. We feel, therefore, that DTC does not cause any permanent change in the chemophysical properties of the cervical mucus, but instead only temporary deterioration during the repair phase.

A new technique for improving cervical factor is described. This technique employs the use of high-dose estrogen at the time that a mature follicle is determined by ultrasound in patients who have inadequate postcoital tests despite the use of low-dose estrogen, guaifenesin, and tetracycline. Previously, a technique based on high-dose estrogen early in the follicular phase was employed; this suppressed pituitary gonadotropins, thus requiring the concomitant use of hMG. Seventy-three percent of the patients for whom this more expensive and intricate technique would have been necessary were able to achieve a good postcoital test through this modified technique of merely using high-dose estrogen when the follicle has already matured. Thirty-three percent achieved a pregnancy within 6 months on this therapy.

A simple and rapid test for the detection of antisperm antibodies of the IgG class on freely swimming spermatozoa in fresh human semen is described. The test is based on the formation of motile mixed agglutinates between erythrocytes sensitized with incomplete anti-Rh-antibodies and freely swimming spermatozoa with surface antisperm antibodies, after mixing both cell types together with anti-IgG antiserum. Agglutination of the red blood cells serves as an internal control. The test can be applied on ejaculates with spermatozoa concentrations down to one million per ml, provided the motility is sufficient. The percentage of motile spermatozoa found to be coated with antisperm antibodies of the IgG class, and the extent of the coating, proved to be correlated with the agglutination titer of circulating antisperm antibodies and with the inhibition of sperm penetration into cervical mucus. The test can be used as a screening for the presence of antisperm autoantibodies in serum and semen.

Previously we have demonstrated that one can significantly improve the cervical factor in cases that have failed with conventional therapy by employing high doses of estrogen to stimulate the cervical mucus glands. The patients are concomitantly treated with human menopausal gonadotropins to stimulate ovulation, because of endogenous gonadotropin suppression by the estrogen. Monitoring of the hMG is accomplished by pelvic sonography. Unfortunately, the serum estradiol assay cannot also be used because it would measure not only endogenous estradiol but also exogenous estradiol from the conjugated estrogens employed. A modification of this technique is described wherein the estrogen now used is ethinyl estradiol. This estrogen has very little cross-reactivity in the 17-beta-estradiol assay. Thus, both ultrasound and serum estradiol monitoring can be used, resulting in a safer and more effective technique.

The in vitro attachment between Escherichia coli and the human spermatozoon was studied using transmission and scanning electron microscopy, and ultracytochemistry. Samples from estrogenized cervical mucus columns containing migrating spermatozoa revealed two types of contact areas: Type I corresponded to the interaction of the bacterial fimbriae with the spermatozoal surface, and Type II, to the intermingling of the eukaryotic and prokaryotic cell glycocalyx. In both types of associations, the attachment area was lanthanum positive and displayed glycoconjugates. These types of intercellular contacts could represent the morphological basis of a mechanism by which bacteria are attached to spermatozoa and are consequently transported to the upper female genital tract.

A review of the immunological implications in reproductive physiology is presented. Although attempts have been made to ascribe the antigenicity of semen to individual components, it has not been possible to isolate the human semen antigen responsible for infertility. In monkeys total ejaculates and seminal plasma have shown higher antigenicity than washed spermatozoa. In bulls some evidence of such antigens have been found in the seminal plasma. They are iron-binding proteins resembling lactoferrin. Most investigators have found no evidence for any participation of the ABO blood group antigens in cases of sterility. On the surface of human spermatozoa histo-incompatibility antigens have been detected. Transplantation antigens may be related to sterility. However, an immulogic tolerance of the maternal organism exists against the genetically foreign fetal tissue. Autoimmune spermagglutinating antibodies have been detected in the sera and in the seminal plasma of males with sterility. An obstruction of the seminal pathways may facilitate the production of such antibodies against retained sperm. Isoimmunity in females against seminal components has been shown in cases of sterility; however, fertile women have also been shown to have such conditions. In a group of infertile women spermagglutination activity was detected in 7.5% of cases. In another series of 46 cases with primary unexplained infertility agglutinating antibodies were found in 17.4%. Other investigators have also reported higher rates than the authors. The sperm immobilization test seems to be more sensitive than the agglutination test. No sera were found positive with both tests. With immunofluorescent techniques humoral sperm antibodies have been found to be the IgM and IgG fractions. Each acts on a different part of the spermatozoa. The only promising therapy against humoral sperm antibodies is avoidance of sperm contact over a long period of time. Reported results have been conflicting. Cortisone did not improve the result. Desensitization or immunosuppresive efforts are of uncertain value.

Three procedures commonly employed in the extraction of soluble proteins from cervical mucus, for the application of the technique for the detection of sperm antibodies also in this biological fluid, were compared in order to establish which provided the highest yield. Studies were therefore carried out on 125 women with primary and secondary sterility characterized by good rheologic qualities of their mid-cycle cervical mucus and in presence of repeatedly poor PCTs, not justified by the seminal characteristics of their partners. The laboratory results and the statistical analysis have shown that as far as concerns IgG, liquefaction with bromelin and solubilization with Baker's buffer provide a better yield than ultracentrifugation; while bromelin alone has the best yield with IgA.

This study describes 4 years of verification of effectiveness and applicability of BBT and symptothermal methods. The couples chosen had to undergo a 6-month-long study phase, and be psychologically motivated and well trained in NFP. During this period, particular emphasis was given to the motivational factor, which was expanded in its anthropological, relational, pedagogical and, sometimes, moral contents. Four hundred and sixty couples entered the program, for a total of 8,140 cycles, in which BBT, cervical mucus, and intercourse were charted. The Pearl Index for unplanted pregnancies was 3.6. Twenty-five unplanned pregnancies occurred in couples using NFP for spacing, and no pregnancies were reported in limiters.

Some factors that may influence the results of studies of breastfeeding behavior in different cultures are identified. Findings of some of the demographic studies of rural areas in the so-called less developed nations are contrasted with studies in urbanized areas of such nations, as well as with studies from developed nations. A review of the physiology of lactation, specifically the role of prolactin is given along with some preliminary findings from the author's ongoing research in Australia.

The effect of the administration of 1-ascorbic acid, either alone or combined with clomiphene, upon induction of human ovulation was investigated in clomiphene-inffective anovulatory women. Oral administration of daily 400 mg of ascorbic acid induced ovulation in two out of five habitually anovulatory cycles and in one out of eight first-grade amenorrhea cases, and was ineffective in all six second-grade hypothalamic amenorrhea cases. Combined administration of ascorbic acid with 5 days of clomiphene induced ovulation in five out of five habitually anovulatory cycles, in 10 out of 17 first-grade hypothalamic amenorrhea cases, and in two out of nine second-grade hypothalamic amenorrhea cases. Pregnancy was established in eight out of 18 sterile, habitually-anovulatory or first-grade amenorrheic women with the combined ascorbic acid-clomiphene therapy, and in one out of five sterile, habitually anovulatory women with ascorbic acid therapy alone. Since administration of ascorbic acid induced no changed in blood FSH, LH, and amount of cervical mucus, and it is well established that LH decreases dose-dependency of the ascorbic acid content in the rat ovaries, the possible site of action of ascorbic acid seems to be at the ovarian level.

The pattern of penetration of human ejaculated spermatozoa into human cervical mucus (HCM) and bovine cervical mucus (BCM) was studied in an in vitro penetration system by means of plate capillary tubes. Sperm penetrate the HCM in a unique pattern making their way progressively forwards in a one-way direction in between the filaments. In contrast, sperm move preferably forward in BCM. The different patterns are probably due to different organizations of the glycoproteins. The penetration values (PV) were also different in the two systems when studied after short periods of incubation (15 and 30 min), but incubation for 1 h brought both systems to the same rate of PV. Thus, this period is enough to overcome the differences between the patterns of penetration. Sperm velocity in semen, in HCM, and in BCM were the same. Cervical mucus (CM) did not affect sperm velocity. A strong correlation (r = 0.8) was found between sperm velocity in the semen and its PV rate either in HCM or in BCM. The results of this study recommend the use of BCM as a reference CM in cross penetration tests and suggest its establishment as a routine method for assessment of sperm quality.

The records of 50 Australian postpartum women who intended to breast-feed for longer than 6 months were analyzed. Fifty percent of the women breast-fed longer than 12 months, and 50% resumed menses by 40 weeks after childbirth. Fifty-four women provided records of mucus and BBT for at least 4 weeks before resumption of menses. Ovulation before menses while fully breast-feeding was probable in only one woman. Fifty percent of the first postpartum cycles had a short luteal phase. Thirty-two women chose NEP to avoid pregnancy during the study period. Mucus and BBT proved to be a good marker of ovulation during postpartum cycles. The mean number of days available for intercourse according to the Ovulation Method was 22.6 days between 6 and 12 postpartum weeks, and 12 days during the 4 weeks before menses. Confidence in NFP during lactational amenorrhoea and first postpartum cycles is analyzed. Finally, research aimed at improving the teaching and use of NFP for postpartum breast-feeding women is described.

Local sperm-agglutinating antibodies (LSAA) in the cervical ovulatory mucus may be a cause of primary infertility. A group of 17 infertile women with LSAA treated without effect with artificial insemination and then condom therapy were studied. After hydrocortisone application to the ectocervix for up to four cycles, LSAA disappeared totally in 13 patients; six of them have given birth to babies. No side effects of treatment were observed. Hydrocortisone for local immunosuppression may become a new method of therapy in cervical immunological infertility.

Sperm antibody titers were evaluated in the serum of 73 infertile couples by the F-D and Kibrick agglutination tests, to study the relationship of the quality of post-coital tests and semen analysis. Thirty-eight couples had poor post-coital tests, fifteen couples had normal post-coital tests, and twenty couples revealed abnormal semen pictures of the males. In the first two groups, semen analysis was normal. The incidence of sperm antibodies was 10.5%, 6.6% in men, and 18.4%, 20.0% in women, with poor and normal post-coital tests, respectively. This suggests that sperm antibody testing is equally indicated in infertile couples with poor post-coital tests. In addition, there was no difference in the incidence of sperm antibodies in men with poor semen pictures and those with normal semen analysis in this infertile population. This suggests the significance of sperm antibody testing in infertile men with abnormal and normal semen pictures after correcting other infertility factors, in order to detect those patients who could benefit from treatment of such immunologic problems.

A new protocol of estrogen-priming and cervical mucus monitoring for individualized hMG therapy was devised. Prior to treatment, the amount of cervical mucus ("a" mm3) should be determined. Then the peak value ("b" mm3) on the amount of cervical mucus resulting from the exogenous 2-day injection of 1 mg of estradiol benzoate is confirmed. After a decrease of the amount of cervical mucus is noted, daily dose of 225(1 - a/b) IU of hMG is administered until the amount of cervical mucus reaches or exceeds the "b" value. hCG is given 36 hours later than the last previous injection of hMG. This new individualized hMG therapy induced 51 ovulations (69.9%), 9 pregnancies (17.6%), and no multiple pregnancies (0%) out of 73 treated anovulatory cycles. This new protocol appears promising for prevention of multiple pregnancy due to hMG therapy, perhaps based on the mechanism of estrogen priming and individualization of both daily dose and duration of hMG administration.

A study was performed to evaluate the relationship between the postcoital test, follicle size, and the basal body temperature (BBT). We found 17% of the patients to have good postcoital tests before the rise in the BBT, at which time, however, the follicle was still too small. By the time the follicle reached maturity, the mucus quality regressed to poor. The problem was corrected in 88% of the patients by the human menopausal gonadotropin (hMG)-high-dose estrogen technique, and 53% achieved pregnancies. Twenty-two percent had a poor postcoital test just before the rise in the BBT. However, ultrasound data indicated that ovulation had already taken place, and the mucus had been of good quality a few days before, when the follicle was at the proper size. Thus, ultrasound may be useful in eliminating false positive and negative cervical factor diagnoses, and is also helpful in some new techniques for treating the cervical factor.

Sperm agglutinating antibodies are purified from sera and cervical mucus of women with unexplained causes of infertility which were positive in the FD-test. Fractionation was performed by affinity-chromatography in a batch device and the sperm agglutinating activity controlled by the Franklin and Dukes test. This sperm antibody fraction was determined via crossed immunoelectrophoresis by migration into an anti-human serum containing gel. In all cases only one big peak resulted. The negative control serum and mucus samples demonstrated no precipitation peaks. By absorption studies it was shown that the sperm agglutinating antibodies in sera were IgM and in cervical mucus IgA. The concentration of IgA and IgM was determined by comparison with standard human IgA and IgM. Thus only one serum- and one cervical mucus antibody seems to be responsible for agglutination. The number of experiments, however, is still too small for general conclusions. This method is easily and quickly performed and can therefore be used as a routine method for the determination of sperm agglutinating antibodies. Its application for sperm-immobilizing or cytotoxic activity remains to be tested.A new technique by which sperm antibodies are purified by affinity-chromatography in a batch device and the sperm agglutinating activity controlled by the Franklin and Dukes (FD) test is described. Specific absorption takes place on an insoluble antigen and desorption reveals purified antibodies. In sera of women with unexplained infertility which were found to be positive to the FD test a specific globulin binding takes place. For quantitative detection of these purified antibodies, crossed immunoelectrophoresis was done. Sera of 4 such infertile women were used. Uterine cervical mucus samples of 3 of them were also examined. As controls, sera negative to the FD test and cervical mucus from the same patients were processed. Spermatozoa were obtained from 15 donors, pooled, washed 3 times with phosphate-buffered saline, and adjusted to spermatozoa content. Cervical mucus was also prepared. Techniques used are given. The method can be easily and quickly performed and therefore used routinely. Antibody fractions, purified by affinity-chromatography migrating against an AHS-containing gel, demonstrated 1 big peak in all 4 of the FD-positive semen samples as well as in the 3 cervical mucus samples. The height of the peak represented a nearly linear relation to the sperm antibody content of the semen. Control samples never showed this peak. By absorption experiments it was found that the protein encountered in serum is IgM and that in cervical mucus IgA. The content of antibodies in the cervical mucus of the same woman was about 1/10 smaller than in her serum. This method is stated to be an improvement over other techniques. Some sperm antibodies are not of the agglutinating type.

Twenty-four couples facing longstanding primary or secondary infertility underwent semen analysis, PCT, functional evaluation of menstrual cycle, hysterosalpingography and laparscopy. All clinical findings were normal with the exception of PCT which was positive in 13 and negative in 11. All the women underwent a multiple approach investigation of local and circulating antibodies production as well as cell-mediated immunity against live spermatozoa. Sperm Immobilization Test (SIT) and Spermatotoxicity Tests (STT) were performed in a single experimental design on cervical mucus and blood serum. Leucocyte Migration Inhibition Test in presence of sperms (LMIT) was done on peripheral leucocytes. Local antispermatic activity in the cervical mucus was negative in all PCT positive cases, and positive in six out of 11 PCT negative cases. SIT and STT were both positive in cervical mucus and in blood in one case only. No correlation could be found between PCT and serum SIT, STT or LMIT. The fertility pattern expressed by the number of pregnancies per years of exposure, already low in the whole group, was even lower in the sub-groups with positive immunological factors. Positive immunological factors do not exclude the possibility of conception but appear to be associated with a reduced rate of conception.

Abnormalities of cervical mucus can have a bearing on a woman's fertility. One means of detecting the presence of such abnormalities is the postcoital test (PCT). As part of a population-based case control study of risk factors for infertility, the reproductive, contraceptive, medical, and sexual histories of women seeking treatment for infertility who had abnormal PCT results were compared with those of fertile controls. A greater proportion of infertile women with an abnormal PCT had previously used a diaphragm than had control women (relative risk (RR) = 3.5, 95% CI = 1.1-11.3). The excess risk associated with use of a diaphragm was particularly high for women who had used one for longer than one year (RR = 7.3, 95% CI = 1.4-37.8), or within one year of attempting to conceive (RR = 5.5, 95% CT = 1.4-22.1). No increased risk was associated with the use of other barrier methods, oral contraceptives, or the intrauterine device.

The records of 227 couples who received artificial insemination by frozen donor semen in 984 treatment cycles were analysed to find out the factors affecting the pregnancy rates. The cumulative pregnancy rate at 6 months was 46.8% and the pregnancy rate per cycle was 10%. The pregnancy rates were adversely affected by (1) increase in the recipient age above 30 years, (2) irregularity of menstrual cycles, (3) the use of clomiphene citrate for induction of ovulation, and (4) low cervical mucus scores. Among our donor semen samples selected with a set of criteria, the sperm counts and initial and post-thaw motility did not affect the pregnancy rates.

Ovulation, defined as the release of a mature oocyte from a ruptured Graafian follicle at the surface of the ovary, is the culmination of the process of follicular maturation. The latter is under the synergistic influence of the pituitary gonadotropins, follicle stimulating hormone (FSH), and luteinizing hormone (LH), the secretion of which is, in turn, stimulated by the hypothalamic decapeptide, LH-releasing hormone (LH-RH). There is a complex interrelationship between the ovarian steroid hormones, estradiol and progesterone, and the gonadotropins, with estradiol exerting both negative and positive feedback effects on the hypothalamo-pituitary unit. Ovulation is triggered by a surge of LH which results from at least two estradiol-induced phenomena, increased hypothalamic production of LH-RH and increased pituitary responsiveness to releasing hormone. Ovulation occurs 16-17 hours following the LH peak and the probability of conception following an act of coitus appears to be maximal 1-2 days prior to ovulation itself. States of anovulation are frequently seen in association with hyperprolactinemia whereas ovulation may be delayed under a variety of circumstances.

Women experienced in cervical self-palpation recognize fertile characteristics when the cervix is high, open, soft, and straight; this happens under estrogenic influence. The cervix is said to show infertile signs when it is low, closed, firm, and lying against the vaginal wall; that change occurs quickly under progesterone influence. The objective of this study was to assess the time relationship among changes in the cervix observed by self-palpation, changes in cervical mucus as observed by women, and the shift in basal body temperature during ordinary cycles. A total of 215 symptothermal charts from natural family planning users were analyzed. The duration of the change from the maximum fertility characteristics to the postovulatory return to definite signs of infertility was measured. This duration ranged from 1 to 7 days, with a mean of 2.65. The timing of maximum fertility signs in the mucus was compared with that of maximum fertility signs in the cervix: it varied from 3 days before to 6 days after, with a mean of 0.48 day. The timing of the first high temperature was compared with that of return to definitely infertile characteristics: it varied from 6 days before to 3 days after, with a mean of -0.69 day. Some of the variation may be due to the presence of inexperienced users in the sample. However, a mean difference of half a day between the most fertile cervix and the most fertile mucus on one hand and between the first day of infertile cervix and the first high temperature on the other hand suggest that the cervical changes could be useful indicators of estrogen and progesterone actions.

The test results of 34 couples, who were previously infertile, in whom a postcoital test (PCT) was performed during the cycle of conception were compared to the scores obtained in a group of patients with cervical factor only infertility (N = 55). Both the mucus scores and number of motile progressive sperm were significantly (P less than 0.001) higher in the previously infertile group compared to those with the cervical factor infertility. The present study suggests that overall, during the cycle of conception, women have PCT scores which are higher than those with cervical factor infertility.

The pattern of change in the levels of prolactin (PRL) in cervical mucus was studied in 19 normal ovulatory women. The concentration of PRL in cervical mucus was generally higher than that in plasma except at midcycle, when a reverse relationship was observed. The concentration of PRL in mucus obtained at midcycle was lower than mucus obtained during follicular phase or luteal phase. There were no significant differences in the total PRL content among preovulatory, midcycle and postovulatory cervical mucus samples. The amount of cervical mucus markedly increased during the periovulatory period (two days from the peak of plasma luteinizing hormone). The cervical mucus PRL level undergoes cyclic changes during the normal menstrual cycle, and the decrease in PRL concentration in mucus at midcycle is most likely a result of the dilutional effect of increased mucus volume. The physiological implication of the presence of PRL in human cervical mucus is also discussed.

Characteristic changes in cervico-vaginal fluid (CVF) volume which occur during the menstrual cycle might be used to detect the fertile phase. Twenty-five normal women were asked to withdraw CVF and measure its volume at home using a small, disposable, graduated vaginal aspirator. In 16 cycles day 0 (ovulation) was defined as the day of maximum follicular diameter according to serial ultrasound examination. A rise in CVF volume occurred between day -9 and -2 and a peak between day -4 and 0. In these sixteen, and in a further 72 cycles, day 0 (time of maximum fertility) was taken as the day of peak cervical mucus secretion. CVF volume rose, on the average, on day -6.2 (range -17 to -2) and peaked on day -0.8 (range -5 to +2). In two cycles, no rise and peak were identified. Changes in CVF volume were easy to recognise and could be useful to couples wishing to achieve pregnancy.

A series of 70 couples with suspected unexplained infertility and who became pregnant after 262 monitored cycles, were reviewed. In each cycle, the postcoital test was scheduled near ovulation time as judged by prior basal body temperature shifts and by cycle length. Postcoital test was graded as excellent, good, fair, bad, and negative. A mean of 26.7% of pregnancy rate per cycle resulted and a mean of 3.74 cycles were needed to obtain a pregnancy. Pregnancy rate was higher (P less than 0.01) for cycles with excellent postcoital test and lower for cycles with bad test. There were no statistically significant differences (P greater than 0.05) in percentage of pregnancies between cycles with either excellent, good, or fair postcoital test. On the other hand, there was statistically significant decrease (P less than 0.05) in the percentage of pregnancies when cycles had bad postcoital test.

Twenty infertile couples with antisperm antibodies in the male or in the female partner were scheduled for treatment. In 15 couples the male and in 5 couples the female partner was the antisperm antibody carrier. In all the couples the result of the in vivo and in vitro sperm-penetration test was negative or poor. The SCMC-test was strongly positive in each of the couples. In all the couples IgG and IgA antisperm antibodies could be demonstrated on the spermatozoa or in the cervical mucus. It was postulated that antisperm IgA and not antisperm IgG is responsible for the penetration reduction of spermatozoa in cervical mucus and for the "shaking phenomenon" in the SCMC-test. Intrauterine inseminations, performed in 20 couples, resulted in four pregnancies. Condom therapy in three couples, for at lest 6 months, had no result. Two men were treated with 96 mg methylprednisolone per day for 7 days; this resulted in a slight decrease of the sperm-agglutination titre, but no pregnancy occurred.

The fertile period of the human menstrual cycle consists of those days on which sexual intercourse can result in a pregnancy. Its duration is determined by the functional life span of the gametes within the female reproductive tract. Various mechanisms control gamete transport and survival in the reproductive tract of the human female. The ovarian hormones estradiol and progesterone have an important role in regulating these mechanisms. The nature of cervical mucus and its governing influences on sperm transport and survival following coitus are of prime importance in defining the fertile days of the menstrual cycle. Man's early concepts of the fertile period were often based on erroneous theories of the female reproductive cycle. It is only since the late 1920's that a true understanding of ovulation and the menstrual cycle has evolved. Current approaches in natural family planning to recognizing the fertile and infertile days of the menstrual cycle are discussed and evaluated.

Preservation of human semen in liquid nitrogen causes a significant impairment of sperm motility. Ejaculated human spermatozoa show an increased motility in the presence of caffeine, a phosphodiesterase inhibitor, and pancreatic kallikrein (EC 3.4.21.8), a kinin-producing proteinase. Hence, the effect of both substances on post-thaw motility, fructose consumption, and cervical mucus penetration of cryo-preserved human spermatozoa was investigated. The results indicate that both substances stimulate the motility of freshly ejaculated spermatozoa and also improve the motility pattern of cryo-preserved human spermatozoa, thus offering a possible means of improving the quality of freeze-preserved human semen.

A three-phase study designed to study the acceptability and use-effectiveness of the modified mucus method covered a sample of 2,601 poor rural migrant women living in eight low-income areas--villages and resettlement slum colonies. In phase I, the women were exposed to NFP awareness, i.e., the modified mucus method, and 61.6% of the women accepted the method, and agreed to learn and use it. The learning phase is three cycles. Of these acceptors, 83.7% were fertile. A large percentage of the acceptors are Hindus. The low acceptance by the Sikhs was who were non pregnant, menstruating cohabiting. 15.3% were nonmenstruating owing to pregnancy or breast feeding; 0.9% were menstruating, but not cohabitating; 35.4% of the women were not interested in learning or using the method. A comparative study of the acceptance and nonacceptance for the selected sociodemographic and family planning variables is analysed. The acceptors of NFP differed significantly from the acceptors of sterilization and IUD in their occupation, educational levels, duration of marriage, number of living children, number of living sons, knowledge of family planning, and previous use of family planning.

Indirect immunofluorescent, macroagglutination and immobilizing sperm antibody estimations were performed as part of a prospective study on a representative group of 63 infertile couples. Serum from both, cervical mucus and seminal plasma were tested and the clinical use of the tests evaluated by considering the pregnancies that occurred and the causes of infertility that were discovered in the subsequent year. The indirect immunofluorescent test had the largest number of positives although more were found in seminal plasma than elsewhere. In these, both male and cervical factors were implicated and in this media there were less positives pregnant with the acrosome and midpiece patterns absent. The macroagglutination test had no positives pregnant and again more significance was attached to positives in the male. Similarly, immobilization results showed most positives in seminal plasma where the male and cervical factors featured prominently. It would, therefore, appear that if any clinical use is to be derived from the three tests in the search for antisperm antibodies as a cause of infertility, testing the male and especially seminal plasma appears to correlate best. If treatment is to be recommended, therefore, it should be concentrated on the man.The significance of sperm antibodies in human fertility was investigated. Indirect immunofluorescent, macroagglutination, and immobilizing sperm antibody estimations were performed as part of a prospective study on a group of 63 infertile couples. The clinical use of the tests was evaluated by considering the pregnancies that occurred and the causes of infertility that were discovered in the subsequent year. The indirect immunofluorescent test showed more positives in seminal fluid (1/3) than elsewhere, although in 62% of the couples at least 1 of the media tested was positive and in 14.3% something was positive in both partners. Both male and cervical factors were implicated, and in this media there were less positives pregnant with the acrosome and midpiece patterns absent. No pregnancies were involved in the positives of the macroagglutination test; in the 3 cases where the male was involved, the cause was asthenozoospermia. The immobilization results showed the greatest number of positives in seminal plasma with male and cervical factors featured prominently. In this group pregnancy was achieved when ovulation was stimulated. It appears that if a clinical use is to be derived from these tests in the search for antisperm antibodies as a cause of infertility, testing the male, and especially seminal plasma, appears to correlate best. If treatment is recommended, it should be for the man.

Results with intrauterine insemination in 25 couples are presented. The indication for this procedure was a cervical factor of infertility. After an extensive fertility survey in both partners, intrauterine insemination was performed four to seven times per cycle with up to 0.8 ml fresh semen per insemination. Only the first ejaculatory spurt was used. Prophylactic antibiotics were given to all female partners during the insemination period. Within a mean of 6 months 13 couples reported pregnancies (52%). Except for one midtrimester abortion that was probably due to obstetrical reasons, the abortion rate was 33.3%. There were no side effects related to the insemination procedure. Our data indicate that, with appropriate safeguards, intrauterine insemination should be regarded as a safe and effective method for the treatment of the cervical factor of infertility.

In 30 or 32 infertile couples with an unexplained negative or bad in vivo and in vitro sperm penetration test, we obtained a strongly positive Sperm Cervical Mucus Contact test (SCMC-test) and demonstrated the presence of antisperm antibodies in the male or female partner. In these 30 couples 25 of the male partners had a sperm-agglutination titre of at least 32 in the serum and at least 4 in the seminal plasma. In the five remaining couples the female partner showed a minimum sperm-agglutination titre of 16 in the serum and a cervical mucus titre of at least 128. In 48 couples with a fair or good sperm penetration in cervical mucus, in vivo and in vitro, we never found a strongly positive SCMC-test. In 43 of these couples the SCMC-test was negative. Only one man in the latter group had sperm-agglutinating activity in the semen. In a group 32 couples, with a negative SCMC-test, there was no or only weak sperm-agglutinating activity in the cervical mucus, although 2 women had moderate sperm-agglutinating activity in the blood serum. Based on these data we conclude that the so called "unexplained" poor postcoital test is almost always due to the presence of antisperm antibodies in the semen or in the cervical mucus. We consider the SCMC-test not only to be a simple and reliable technique for detecting the presence of these antisperm antibodies, but also a method of demonstrating the mechanism by which antisperm antibodies decrease the chance of conception.

A study of the correlation between results of postcoital tests (PCTs) and presence of sperm antibodies in sera of either male or female partners or in the cervical mucus of seminal plasma, was made in 127 infertile couples. The percentage of positive antibody tests increased progressively as PCT results deteriorated from excellent to poor. Thus, the percentage of positive serum tests, by either method used, was 7% in the excellent group as compared to 52% in the poor group. This progressive increase was evident only in the females; the antibody tests in the males did not correlate directly with the PCT results. Nonetheless, even with excellent PCT results, 7% of women and 21% of men showed presence of antibodies. On the other hand, in the group showing poor PCTs, 48% of women had an absence of antibodies.

Cervical mucus is a complex secretion produced by the endocervical epithelium. A comparative analysis of 30 enzymes was carried out on 15 women during their periovulatory period (days 10 to 16 of the menstrual cycle). Nine different enzymes were always found to be present in the cervical mucus. Changes in enzymatic activity were further studied in two of the women, one with a normal (27-day) and the other with a short (20-day) menstrual cycle. The data were compared with those for the same enzymes in the saliva of these two women. Each woman's ovulation time was determined through hormone measurements in urine and blood, as well as by recording basal body temperature and by Billing's method. Our results indicate that a maximum peak occurs for several enzymes during the periovulatory period.

Estrous bovine cervical mucus (BCM) was evaluated as a practical substitute for midcycle human cervical mucus (HCM) in the sperm-cervical mucus penetration technique (S-CMPT). Analysis of semen samples from 299 men of infertile couples suggested that up to 95% of the S-CMPT analyses with BCM were compatible with results expected with HCM. Results from a secondary S-CMPT with BCM using donor sperm treated with seminal plasma or cervical mucus extracts from partners of infertile couples indicated 70 and 88% agreement with the clinical S-CMPT obtained with the semen and cervical mucus samples, respectively. Seminal plasma samples from men with serum antisperm antibodies decreased the ability of donor sperm to penetrate BCM in the Secondary S-CMPT. Our results indicate that estrous BCM possess those basic qualities of HCM that support human sperm motility, allow for normal sperm penetration, and interact with antibody-treated sperm to inhibit penetration and to produce the sperm shaking phenomenon.