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Greater than expected fertility decline in Ghana: untangling a puzzle.

This study examines fertility decline that is larger than expected on the basis of recorded increases in contraceptive prevalence in Ghana. The primary sources of data are three Demographic and Health Surveys (DHS) conducted in the country in 1988, 1993 and 1998. First, the trend in fertility and contraceptive prevalence in Ghana is considered and compared with the trend that would be expected on the basis of prior research. Next, an attempt is made to uncover the explanation behind this unexpected trend. Measures of the quality of the survey data are looked at, as well as trends in the proximate determinants of fertility: contraceptive use, marriage and sexual activity, postpartum insusceptibility and induced abortion. Finally, evidence is presented that couples adjust their coital frequency in accordance with their fertility preferences, behaviour that would influence fertility rates but would not be captured by conventional measures of the proximate determinants of fertility.

Abortion, Therapeutic↗

Presence of cumulus cells during in vitro fertilization protects the bovine oocyte against oxidative stress and improves first cleavage but does not affect further development.

The present study was conducted to evaluate the function of cumulus cells during bovine IVF Oocytes within cumulus-oocyte complexes (COCs) or denuded oocytes (DOs) were inseminated in control medium, or DOs were inseminated in cumulus cell conditioned medium (CCCM). DOs exhibited reduced cleavage and blastocyst formation rates when compared with intact COCs. The reduced blastocyst formation rate of DOs resulted from reduced first cleavage but subsequent embryo development was not changed. Live-dead staining and staining for apoptotic cells revealed no differences in blastocysts from oocytes fertilized as COC or DO. Fertilization of DOs in CCCM partially restored the cleavage rate, suggesting that factors secreted by cumulus cells are important for fertilization but that physical contact between oocytes and cumulus cells is required for optimal fertilization and first cleavage. Exposure of COCs to hydrogen peroxide shortly before fertilization reduced the cleavage rate, but did not lead to enhanced death of cumulus cells or oocyte death. Exposure of DOs to hydrogen peroxide, however, resulted in oocyte death and a complete block of first cleavage, suggesting that cumulus cells protect the oocyte against oxidative stress during fertilization.

Animals↗

The status of controlled prospective clinical trials for efficacy of intracytoplasmic sperm injection in in vitro fertilization for non-male factor infertility.

PURPOSE: Intracytoplasmic sperm injection (ICSI) of some sibling oocytes may have a beneficial effect in couples going through in vitro fertilization for causes of infertility not related to the male factor. Our purpose was to critically appraise the randomized controlled studies done in this area and arrive at some recommendations. METHODS: The four controlled trials done so far have utilized similar methodology, i.e., they randomly allotted sibling oocytes to ICSI versus standard insemination in patients going through in vitro fertilization and embryo transfer. RESULTS: In the first trial reported in 1995 there was no difference in fertilization rate, whereas the later trials reported in 1997, 1999, and 2000 showed improvement with ICSI that reached statistically significant level in the last two studies. CONCLUSIONS: Total fertilization failure of an in vitro fertilization cycle can be prevented and fertilization can be improved if half of sibling oocytes are subjected to ICSI.

Controlled Clinical Trials as Topic↗

Effects of reducing insemination time in human in vitro fertilization and embryo development by using sibling oocytes.

PURPOSE: Recent studies showed a beneficial effect of reducing the time of sperm-oocyte interaction on fertilization, division, and implantation rates of the oocytes obtained from randomized patients. In the present study, the effects of reduced insemination time on fertilization and embryo development were evaluated by using sibling oocytes from the same patient. METHODS: A total of 464 oocytes from 36 patients was randomly allocated to be inseminated for either 1 hr (reduced) or 18 hr (regular). RESULTS: Fertilization rates were not significantly different between reduced (135/229; 59%) and regular (150/235; 64%) groups. Cleavage rates and embryo quality were similar in both groups. A total of 135 embryos (73 from the reduced and 62 from the regular group) was transferred to 36 patients. Thirty-four embryos implanted in 18 patients (25.2% implantation and 50.0% pregnancy rates). CONCLUSIONS: Fertilization, cleavage, and embryo development from 1-hr insemination is comparable, not superior, to those from an 18-hr insemination time, which is commonly used in in vitro fertilization programs. These data suggest that reduced insemination time can be used during in vitro fertilization to avoid unnecessarily longer exposure to spermatozoa.

Adult↗

Dual ionic controls for the activation of protein synthesis at fertilization.

The general metabolic activation of the sea urchin egg at fertilization is dependent on a release of intracellular stores of calcium and the subsequent transient elevation of intracellular Ca2+ (refs 1--3). However, this elevation does not by itself lead to increased macromolecular synthesis and development but initiates steps which result in a long-term elevation of intracellular pH (refs 4--6). Among the developmental processes dependent on the elevation of intracellular pH is the large acceleration in the rate of protein synthesis at fertilization. Weak penetrating bases such as ammonia can be used to mimic the processes resulting in an increase in intracellular pH and so show the corresponding increases in protein synthesis rate. Conversely, it is possible to demonstrate a gradual but complete shut down of protein synthesis if the intracellular pH is reduced to the unfertilized level with penetrating weak acids. However, the rate of protein synthesis in ammonia-activated eggs lags behind that of fertilized controls even though ammonia activation can result in an intracellular pH increase greater than occurs in the fertilized egg. This result has led to the suggestion that factors other than intracellular pH may be regulating protein synthesis following fertilization. To investigate the possibility that the Ca2+ transient may have such a role, we measured the rate of amino acid incorporation in eggs that were activated in various ionic conditions which enabled the effects of Ca2+ and pH changes to be studied separately. Our results, reported here, show that if intracellular pH is elevated, increases in intracellular Ca2+ play an additional part in the activation of protein synthesis at fertilization.

Animals↗

The role of fertility restoration in the maintenance of the inversion In(2L)t polymorphism in drosophila melanogaster.

In order to explain the worldwide latitudinal distribution and seasonal fluctuations in In(2L)t frequencies in Drosophila melanogaster, fitness differences among In(2L)t and Standard (ST ) homo- and heterokaryotypes under high-temperature conditions were determined. Viabilities were measured for high-temperature treatment started at different juvenile stages. The capacity to restore fertility after high-temperature treatment was measured for adults and juveniles. Furthermore, genetic adaptation for increased temperature resistance for these traits was determined for strains which were reared at 33 degrees C for 10 generations. Whereas larva-pupa survival rates were high, highest juvenile mortalities and strongest karyotypic effects were observed during the pupal stage when preceding larval stages were reared at 33 degrees C. ST karyotypes showed lowest viabilities. Although mating rate was hardly influenced, sterility was induced for females and males after high-temperature treatment of adults as well as juveniles. Subsequent transfer to 25 degrees C, however, resulted in restored fertility in some of the individuals, depending on the length of the recovery period. Fertility restoration was significantly higher for heterokaryotype males and females. Heterokaryotype superiority for restored fertility as well as for viability was positively correlated with severity of the treatment. Ten generations of selection at 33 degrees C resulted in significant improvement of juvenile survival and fertility restoration for all karyotypes. These fitness components were positively correlated (r=0.91; P < 0.001), which might suggest pleiotropic effects. It is concluded that the capacity to restore fertility after heat stress is an important fitness component, especially with respect to the In(2L)t polymorphism. The observed heterokaryotypic superiority fits with the idea that the latitudinal distribution of In(2L)t frequencies is maintained by balancing selection, with equilibrium values decreasing with latitude.

Animals↗

Comparison and evaluation of laboratory performance on a method for the determination of perchlorate in fertilizers.

This report details the interlaboratory validation of a method for the determination of perchlorate in fertilizers. In this method (EPA/600/R-01/026), a solid sample of fertilizer is ground. Subsequently, the ground material is either leached with deionized water to dissolve any perchlorate salt in the case of minimally soluble fertilizers (e.g. supertriplephosphate or timed-release products), or simply dissolved in the case of highly soluble fertilizers (e.g. urea, NaNO3 or KCl). The resulting aqueous solution is then subjected to ion chromatography with suppressed conductivity detection. Four laboratories applied the method to field samples of 48 different products (commodity chemicals) and to seven quality control samples prepared by the Environmental Protection Agency (EPA). Additional tests were conducted by three other laboratories on specific materials. Recovery (81-111%) was demonstrated on spikes of known concentration, and a preliminary assured reporting level was determined for each fertilizer matrix by each laboratory. Injection-to-injection precision was satisfactory: generally less than 15% difference, and always less than 25%. All of the laboratories used Dionex IonPac AG16 guard and AS16 separation columns with NaOH or KOH as eluent. Detection was by suppressed conductivity. The method was shown to be sufficiently robust for the screening of fertilizers for perchlorate, but performance was low on a mixture of siliceous minerals (kaolinite and bentonite). Both laboratory performance and method performance are validated.

Calibration↗

Performance of poly(vinyl alcohol) gel columns on the ion chromatographic determination of perchlorate in fertilizers.

Interest in possible sources of perchlorate (ClO4) that could lead to environmental release has been heightened since the Environmental Protection Agency placed this anion on its Contaminant Candidate List for drinking water. Although recent investigations have suggested that fertilizers are minor contributors to environmental perchlorate contamination overall, there is still interest in screening commercial products for possible contamination and quantitating perchlorate when it is found. Ion chromatography (IC) has been used for this application owing to its speed, low detection limits, widespread availability, and moderate ruggedness relative to other techniques. However, fertilizer matrixes complicate the IC analysis relative to potable water matrixes. In this study, the performance of poly(vinyl alcohol) gel resin IC columns (100 mm and 150 mm) was evaluated for fertilizer matrixes using method EPA/600/R-01/026. The NaOH eluent included an organic salt, sodium 4-cyanophenoxide. Detection was by suppressed conductivity. A set of 55 different field samples representing 48 products and previously used by the EPA to assess occurrence of perchlorate in fertilizers (EPA/600/R-01/049) was reanalyzed on the 150 mm column. The 100 mm column was used to further investigate the positive hits. Both columns gave satisfactory performance in fertilizer matrixes, with spike recoveries (+/- 15%), assured reporting levels (0.5-225 microg g(-1) except for one at 1,000 microg g(-1)), accuracy (relative error < 30% always and most < 15%), and precision [injection-to-injection reproducibility < 3% relative standard deviation (RSD)] comparable to those reported in other studies. Performance did not vary substantially between column lengths. Lastly, the results of this investigation provided further evidence in support of the conclusions that had been reached previously by the EPA on the occurrence of perchlorate in fertilizers.

Chromatography, Ion Exchange↗

Effect of freeze-thawing procedure on chromatin stability, morphological alteration and membrane integrity of human spermatozoa in fertile and subfertile men.

Cryopreservation is known to impair sperm motility and decrease the fertilization rate by detrimental effects on acrosomal structure and acrosin activity. However, the consequences of cryopreservation on the integrity of the sperm nucleus, chromatin stability and centrosome are less clear. The present study was designed to determine the effect of the freeze-thawing procedure on chromatin condensation (aniline blue staining) and the morphology (strict criteria) and membrane integrity of human spermatozoa. The structural and functional characteristics of the sperm plasma membrane were measured by the eosin-test and hypo-osmotic swelling test which were done separately. Sperm cryopreservation was performed on semen samples from two groups of men classified as fertile (n = 20) and subfertile (n = 72), based on their reproductive history and semen analysis according to WHO guidelines. The mean percentage of condensed chromatin, morphologically normal spermatozoa and membrane integrity in all semen samples investigated (n = 92) decreased significantly (p = 0.0001) after freeze-thawing, in comparison to the value observed prior to freezing. By comparing the semen samples between fertile and subfertile patients, significantly (p = 0.0009) greater damage was demonstrated in the subfertile than in the fertile group. Furthermore, no significant difference was observed between the two groups with regard to the morphological alteration and structural as well as functional damage of the sperm membrane. In conclusion, the freeze-thawing procedure significantly affects chromatin structure and sperm morphology, especially in the head and the tail regions, and this may explain the lower fertilization rate and IVF/ICSI outcome when frozen-thawed spermatozoa are used. In addition, this study demonstrates that chromatin condensation is a sensitive parameter for the evaluation of cryodamage of semen samples from fertile and subfertile patients, though subfertile patients with very poor semen characteristics have yet to be studied. It is therefore recommended that chromatin condensation be used as an additional parameter for the assessment of sperm quality after freeze-thawing.

Cell Membrane↗

Effect of hyaluronan on monospermic penetration of porcine oocytes fertilized in vitro.

An experimental series was carried out to examine the ability of exogenous hyaluronan (HA) to facilitate monospermic penetration of in vitro-matured (IVM) oocytes during conventional porcine in vitro fertilization (IVF). IVM oocytes were co-cultured in fertilization medium with frozen-thawed, ejaculated boar spermatozoa. Addition of 0.5 mg/mL HA to the fertilization medium increased the rates of monospermic penetration (p < 0.05) on cumulus-denuded oocytes, without detrimentally affecting penetration rates (rates of monospermy were 57% and 78% in 2 mM caffeine-containing fertilization medium without and with HA, respectively). Caffeine and cumulus cells affected the rate of monospermic fertilization (p < 0.02-0.03), and caffeine affected the rate at which oocytes were penetrated (p < 0.02). Moreover, exogenous HA (0.5 mg/mL) in the sperm pre-incubation medium promoted monospermic penetration rates without affecting overall penetration rates. The effects of exogenous HA on sperm penetration and monospermy were also compared among semen batches. After semen was pooled from three fertile boars and held in homologous seminal plasma (SP) for 3 (batch A), 10 (batch B) or 20 (batch C) h prior to being cooled, spermatozoa from each semen batch were co-cultured with IVM oocytes. Monospermy of cumulus-denuded oocytes was increased (p < 0.05) by the addition of exogenous HA within the same semen batch (batches B and C). Furthermore, co-culture with cumulus cells did not mask the effects of HA on batch-B semen. The concentration of exogenous HA (0, 0.05 and 0.5 mg/mL) during sperm-oocyte co-culture differentially affected the rates of penetration and monospermy of cumulus-intact oocytes, depending on the time spermatozoa were held in SP before being frozen. The highest penetration rate was obtained by exposing semen to SP for 20 h prior to being cooled (0.05 mg/mL HA). The results suggest that exogenous HA decreases polyspermy during conventional porcine IVF. Furthermore, it appears that the action of HA is dependent upon the priming action of seminal plasma.

Animals↗

Characterization of the fertility of Kit haplodeficient male mice.

The role of the proto-oncogene Kit expression during gonadal development, then in differentiated spermatogonia has been thoroughly established. The present study was designed to investigate the consequences of a partial defect in Kit gene expression on sperm fertilizing ability, using Kit haplodeficient mice (kitW-lacZ/+). Same inbred mice (kit+/+) were used as controls. Epididymal sperm characteristics and in vivo fertility were assessed, then in vitro-fertilization experiments were carried out for mice of both genotypes. Epididymal sperm count was drastically reduced, and sperm motility was also decreased in kitW-lacZ/+ compared with kit+/+ males. Both in vivo or in vitro fertility were greatly reduced in kitW-lacZ/+ compared with kit+/+ males. By contrast, the fertility of kitW-lacZ/+ females was apparently unaffected. Additionally, a higher number of spermatozoa with undetected acrosomal contents was revealed by fluorescein isothiocyanate-labelled Pisum sativum agglutinin acrosomal staining after epididymal sperm retrieval in kitW-lacZ/+ mice, whereas no difference was observed after induction of acrosomal reaction in mice of either genotype. Ultra-structural data confirmed the higher frequency of abnormal acrosome in spermatozoa of kitW-lacZ/+ mice. Thus, sperm production is impaired in Kit haplodeficient mice both on a quantitative and a qualitative basis. Finally, we show that one single copy of Kit gene is not sufficient to maintain genuine fertility in male mice.

Animals↗

Laboratory semen assessment and prediction of fertility: still utopia?

Finding a laboratory test reliable enough to predict the potential fertility of a given semen sample or a given sire for artificial insemination (AI) is still considered utopian, as indicated by the modest correlations seen between results obtained in vitro and field fertility. Male fertility is complex, and depends upon a heterogeneous population of spermatozoa interacting at various levels of the female genital tract, the vestments of the oocyte, and the oocyte itself. For this reason, laboratory assessment of semen must include the testing of most sperm attributes relevant for fertilization and embryo development, not only in individual spermatozoa but within a large sperm population as well. Strategies for the discovery of in vitro predictors of semen fertility require evaluations of low sperm doses for AI, so that differences in innate in vivo fertility can be accurately detected.

Animals↗

Sonographic early fetal gender assignment: a longitudinal study in pregnancies after in vitro fertilization.

OBJECTIVES: A longitudinal evaluation by sonography of external genitalia in human embryos/early fetuses with a known time from fertilization is lacking. Our aim was to assign by sonographic evaluation of external genitalia the early fetal gender in a cohort of pregnancies after in vitro fertilization. Sonographic examinations were performed in each case in three subsequent sessions over a period of time early in gestation in order to establish a temporal threshold, expressed in terms of days from fertilization, at which absolute accuracy in gender prediction is achievable. METHODS: Thirty-two fetuses were included in this prospective longitudinal study. Each was examined three times for gender assignment. The first observation was performed between 65 and 69 days from fertilization, the second between 70 and 74 days and the third between 75 and 79 days. Transvaginal and/or transabdominal sonography was used to detect the 'sagittal sign' as a marker of fetal gender. The results of ultrasound examinations were compared with gender at birth or with karyotype obtained from amniotic fluid cells or chorionic villus sampling. RESULTS: Fetal gender assignment was feasible in 29 out of 32 fetuses (90%) at the first examination and in all cases at the second and third examinations. Fetal gender prediction was correct in 76% of cases in which fetal gender was assigned (22/29) at the first examination; accuracy for males was 46% (6/13) and for females 100% (16/16). At the second and third examinations, accuracy for gender prediction achieved 100% for both genders. Concerning the temporal threshold, absolute accuracy in gender prediction was achieved at 69 days from fertilization, corresponding to 11+6 weeks based on the last menstrual period. CONCLUSION: This study provides important information about the earliest stage, expressed in terms of days from fertilization, at which it is possible to make a certain diagnosis of fetal gender by sonography.

Female↗

The effect of cooling rate before freezing and the temperature of the semen upon addition of DMSO on the fertilizing capacity of chicken semen stored at - 196 degrees C.

Semen was collected from Single Comb White Leghorn roosters, diluted 1:4 with Beltsville Poultry Semen Extender at 35 degrees C and cooled at various rates to 5 degrees C. DMSO was added to the semen between 10 and 120 min after ejaculation at temperatures between 15 and 5 degrees C, respectively. Following the addition of DMSO, the semen was allowed to equilibrate for 2 h in a 5 degrees C environment. The semen was then frozen at 1 degree C per min from 5 degrees C to - 20 degrees C, transferred into liquid nitrogen vapour for 4 to 10 min and then immersed in liquid nitrogen for 4 to 60 days. The thawed semen was inseminated on two consecutive days and fertility was calculated during 5 and 7 days commencing on the second day after the last insemination. In general, fertility was unaffected by the rate of cooling and the temperature at which the DMSO was added. In one trial, however, the fertilizing capacity was significantly greater if the DMSO was added within 45 min when the temperature of the semen was 15 degrees C. Approximately 42 to 71 p. 100 of eggs laid by hens during the 5 day period after the second insemination were fertile regardless of the method of cooling or the temperature of the semen when the DMSO was added. The motility of the ejaculates after thawing and before insemination varied between 15 and 55 p. 100 and this measure of physiological quality was a poor indicator of fertilizing capacity. Embryonic mortality was unaffected by the cooling and freezing procedure and hatchability of fertile eggs was not significantly different for the hens inseminated with either fresh or frozen semen.

Animals↗

Fertility of ram spermatozoa pellet-frozen in zwitterion-buffered diluents.

The fertility (positive ultrasound scanning 60-75 days after insemination) of ram spermatozoa frozen in Tris- or zwitterion/glucose/egg yolk/glycerol-based diluents was examined during the natural breeding season (autumn). In Experiment 1 Tris-citrate, high glucose and Hepes-NaOH diluents were used and ewes (n = 266) were inseminated (induced oestrus) with 20 (uterus) or 180 (cervix) million motile spermatozoa. There was no difference in fertility (range: 10.9-71.1%) between diluents, despite the superior post-thawing motility and progressive velocity of spermatozoa in Hepes-NaOH compared with the other diluents (P < 0.001). In Experiment 2, there was no difference in fertility (range: 4.1-50.0%) between Tris-citrate and Hepes-NaOH diluents after insemination (induced oestrus) of ewes (n = 290) with 10 (uterus) or 100 (cervix) million motile spermatozoa, respectively. In Experiment 3 Tris-citrate, Hepes-NaOH and Pipes-NaOH diluents were used and ewes (n = 492) were inseminated (natural oestrus) with 8 or 24 (uterus), or 80 or 240 (cervix) million motile spermatozoa. There were no differences in fertility (range: 35.4-52.9%) between insemination doses or diluents despite the superior motility and acrosome integrity in the zwitterion compared with the Tris-citrate diluents (P < 0.001). In all experiments, the fertility of frozen spermatozoa was higher for intrauterine than cervical insemination (51.9 vs 22.1%, n = 1 048; P < 0.01). It was concluded that post-thawing in vitro quality was superior and the fertility comparable after freeze-thawing spermatozoa in zwitterion compared with Tris-citrate diluents.

Animals↗

Some semen abnormalities may cause infertility by impairing implantation rather than fertilization.

The hypo-osmotic swelling (HOS) test measures the functional integrity of the sperm membrane. Although, the sperm membrane is essential for the fertilization of oocytes, several clinical studies suggest that abnormally low HOS test scores do not predict poor or failed fertilization in human in-vitro fertilization trials. However, in-vivo and in-vitro studies clearly demonstrate that a low HOS score is associated with poor pregnancy rates suggesting this sperm defect causes implantation problems rather than fertilization problems. The problem of implantation could be caused by the supernumerary sperm attached to the zona pellucida. Supporting evidence for this theory was demonstrated by finding high pregnancy and implantation rates despite low HOS scores following intracytoplasmic sperm injection which avoids the presence of supernumerary sperm on the zona pellucida. These data thus support theories that some sperm abnormalities may reduce fertility potential by causing implantation disorders rather than problems with fertilization.

Abortion, Spontaneous↗

[Ovarian stimulation in an in-vitro fertilization programme].

The in-vitro fertilization of human ova and the subsequent transfer of the embryo are a possibility for infertile patients with damaged fallopian tubes to achieve a pregnancy. The results of different methods of ovarian stimulation in an in-vitro fertilization programme are described. The Clomiphen/hCG treatment and the overlapping Clomiphen/hMG/hCG treatment were used. Between July 1982 and March 1983, 130 patients had a laparoscopic aspiration of ovarian follicles at the Department for Obstetrics and Gynaecology in Luebeck. 585 follicles were aspirated and 404 ova retrieved. 210 showed the criteria of a preovulatory ovum. Of these 210, 177 were fertilized. In 95 patients an embryo transfer at the 2-8 cell stage was carried out. Inspite of the good fertilization rate of over 80% and the good embryo transfer rate of over 70%, pregnancy was achieved only in 13 cases. The number of follicles and of the retrieved preovulatory ova as well as the fertilization rate were best in the group which received combined Clomiphen and hMG. The pregnancy rate was not different compared to the other group. The first delivery of a healthy infant following laparoscopic aspiration of a follicle and in-vitro fertilization and embryo transfer in Luebeck occurred in March 1983.

Adult↗

Fertility in men exposed prenatally to diethylstilbestrol.

BACKGROUND: Prenatal exposure to diethylstilbestrol causes infertility in male mice and has been associated with malformations of the genital tract in men. However, little is known about the fertility of men who have been exposed prenatally to diethylstilbestrol. METHODS: In 1950 through 1952, 1646 pregnant women were enrolled in a randomized, placebo-controlled clinical trial of diethylstilbestrol at Chicago Lying-in Hospital. We interviewed men who were born to the women during that study about their fertility. RESULTS: Four decades after their birth, we were able to trace 548 of the surviving sons (68 percent). Ninety percent consented to be interviewed (253 who had been exposed to diethylstilbestrol in utero and 241 who had not been exposed). Congenital malformations of the genitalia were reported three times as often by the diethylstilbestrol-exposed men as by the sons of the women in the placebo group. Within the exposed group, malformations were reported twice as often among those exposed to diethylstilbestrol before the 11th week of gestation as among those exposed later (P = 0.05). Men with genital malformations were nonetheless as fertile as other men. The diethylstilbestrol-exposed men (with or without genital malformations) had no impairment of fertility by any measure, including whether they had ever impregnated a women, age at the birth of their first child, average number of children, medical diagnosis of a fertility problem, or length of time to conception in the most recent pregnancy of the female partner. Finally, diethylstilbestrol-exposed men had no impairment of sexual function, as indicated, for example, by the frequency of intercourse or reported episodes of decreased libido. CONCLUSIONS: High doses of diethylstilbestrol did not lead to impairment of fertility or sexual function in adult men who had been exposed to the drug in utero.

Abnormalities, Drug-Induced↗