Cervical mucus score and in vitro sperm mucus interaction in spontaneous and clomiphene citrate cycles

OBJECTIVE: Assessment of the effects of clomiphene citrate (CC) on cervical mucus score and in vitro sperm mucus interaction. DESIGN: Prospective study of cervical mucus score and in vitro sperm mucus interaction in a spontaneous cycle followed by a CC cycle to compare paired data. SETTING: Tertiary institutional infertility clinic. PATIENTS, PARTICIPANTS: Twenty-two couples with primary unexplained infertility were studied in both cycles. INTERVENTIONS: Clomiphene citrate (150 mg) on days 5 to 9 in CC cycles. MAIN OUTCOME MEASURES: Cervical mucus score and sperm-mucus penetration test score. RESULTS: Mean cervical mucus score in spontaneous cycles was 9.3 (95% confidence interval [CI] 8.4 to 10.2) and in CC cycles 5.6 (95% CI 4.6 to 6.6), P less than 0.0001. Sperm-mucus penetration test score in spontaneous cycles was 11.4 (95% CI 7.6 to 15.2) and in CC cycles 3.9 (95% CI 1.17 to 6.63), P less than 0.01. CONCLUSIONS: Clomiphene citrate has an adverse effect on both cervical mucus score and sperm-mucus penetration.     

Mechanisms of filtration of morphologically abnormal human sperm by cervical mucus

It is well known that cervical mucus restricts penetration of morphologically abnormal human sperm, both in vitro and in vivo. However, the mechanisms of such restriction are not well understood. Using videomicrography to simultaneously analyze the motions and morphology of individual human sperm, we analyzed differential penetration of normal and abnormal sperm into fresh human cervical mucus. Abnormal sperm swam slower in mucus than the normal sperm, but their flagellar beat parameters were not commensurately different. Multivariate statistical analysis of the relationship between individual sperm velocity and flagellar beat parameters indicated that the heads of the abnormal sperm experienced greater resistance from the mucus than did normal heads. Differential mucus resistance, more than altered motile vigor, appears to be responsible for the restriction of abnormal sperm during migration through mucus.     

Ultrasonographic assessment of endocervix and cervical mucus in ovulatory menstrual cycles

OBJECTIVE: In addition to the routinely used methods to evaluate the menstrual cycle, a new method will be described, assessing the aspect of the endocervix and the presence of cervical mucus by transvaginal ultrasonography. STUDY DESIGN: 36 healthy female volunteers with regular menstrual cycles participated in the study. Transvaginal ultrasonography was performed every other day until ovulation was observed, assessing the diameter of the largest ovarian follicle, endometrial thickness, the aspect of the endocervix, and the presence of cervical mucus. On the same days serum hormone concentrations were determined. RESULTS: Changes in the echodensity of the endocervix were observed in 35 volunteers, from 7 (1-19) (median and range) days before ovulation onwards. The presence of cervical mucus could clearly be observed in the preovulatory phase in 25 volunteers, from 3 (1-7) days before ovulation onwards. CONCLUSION: Preovulatory changes in the aspect of the endocervix and cervical mucus can be observed by transvaginal ultrasonography. Ultrasonography of the cervix may offer an additive diagnostic tool in fertility disorders and will, in many cases, make visual inspection of the cervix unnecessary.     

Behavior of preovulatory markers in normal and abnormal cycles

Various ovulation markers in natural cycle (ultrasound measurement of follicular diameter, E2, progesterone, and LH assays) have been studied in 18 women. The patients were divided into two groups. Group 1: women who became pregnant during the same cycle; group 2: women who showed evidence of follicular growth, E2 and a LH midcycle rise, but low P levels in the luteal phase. A weaker increase in these parameters was found in group 2, especially the LH rise. Moreover, an asynchronicity between the endocrinological and morphological events has been observed in the suboptimal cycles. These findings suggest a process of follicular atresia at the end of the maturation phase, as is commonly found in otherwise normal women.     

Endometrial volume change during spontaneous menstrual cycles: volumetry by transvaginal three-dimensional ultrasound

Objective: At present, only limited data are available on endometrial volume during the menstrual cycle. Most of these studies deal with animal models and use magnetic resonance imaging for volume measuring. The application of three-dimensional ultrasound in endometrial volume estimation is the subject of this study.Setting: Patients visiting the outpatient unit of the division of endocrinology and reproductive medicine of a university hospital.Patient(s): Twenty patients with a history of a normal menstrual cycle were selected.Intervention(s): Ultrasound examinations were performed during a single menstrual cycle in addition to routine laboratory tests.Main Outcome Measure(s): Uterus-endometrial volume ratio.Result(s): Data from 18 patients could be evaluated. In 81 examinations the endometrium volume could be determined. Mean endometrial volume measured by three-dimensional ultrasound was 1.23 cm'. Mean uterus volume was 48.93 cm3. The change of the uterus-endometrial volume ratio showed a good correlation with the day of menstrual cycle. Quadratic regression analysis of volume and cycle length was R² = 0.432.Conclusion(s): Three-dimensional ultrasound allows assessment of volume data of the female internal genitalia. In this study changes of the endometrial volume in menstrual cycles were measured. Additional studies are required to give information on the clinical impact of this new technique of endometrial volume estimation.     

Sensitivity and specificity of ultrasound indices of ovulation in spontaneous cycles

OBJECTIVE: Evaluation of sensitivity and specificity of 4 ultrasound indices of ovulation. STUDY DESIGN: Multicenter collaborative study of 794 abdominal and transvaginal ultrasound scanning of ovaries performed during 271 cycles in 107 normally fertile women. Comparison of sensitivities and specificities of indices using McNemar test. RESULTS: The sensitivity and specificity of the indices were 84 and 89.2, respectively, for disappearance or sudden decrease in follicle size; 38.4 and 79.7 for appearance of ultrasonic echoes in the follicle; 61.6 and 87.1 for irregularity of follicular walls; 71.0 and 88.2 for appearance of free fluid in the cul-de-sac of Douglas. CONCLUSION: Ultrasonic echoes had a significantly lower sensitivity (P<0.001) and specificity (P<0.01) than other indices.     

Monitoring of in vitro fertilization-embryo transfer cycles by ultrasound versus by ultrasound and hormonal levels: a prospective,multicenter, randomized study

OBJECTIVE: To determine whether cycle monitoring using both serum E(2) and ultrasound findings yields superior clinical pregnancy rates during IVF-embryo transfer (ET) compared to monitoring with ultrasound alone. DESIGN: Prospective, randomized, multicenter, patient-blinded study. SETTING: Four assisted conception units in the United Kingdom. PATIENT(S): Two hundred ninety-seven women believed to be normal responders undergoing IVF treatment. INTERVENTION(S): Patients were randomly allocated on day 7 of stimulation to one of the two hCG administration criteria: [1] the E(2)-to-follicle > or =11 mm ratio was between 250 and 500 pmol/L/follicle and at least 2 follicles reached a mean diameter of 18 mm or [2] at least 2 follicles reached a mean diameter of 18 mm and the endometrium thickness was > or =8 mm. MAIN OUTCOME MEASURE(S): Duration and cumulative dose of recombinant human FSH, total number of growing follicles, oocytes retrieved, number and quality of embryos, pregnancy rates, and ovarian hyperstimulation syndrome (OHSS) rates. RESULT(S): Two hundred ninety-seven patients were randomized to one of the two criteria groups. Of these, 288 (97%) received urinary (u)-hCG (143 in group A and 145 in group B). One hundred three women in group A (72%) met both criteria for hCG administration. Pregnancy and OHSS rates were similar (34.3% vs. 31.4% and 4.9% vs. 4.1%, respectively). CONCLUSION(S): The addition of E(2)/follicle criteria to ultrasound monitoring of IVF cycles in normal responders seldom changes the timing of hCG, and does not increase pregnancy rates or the risk of OHSS.     

Treatment of cervical ectropion by cryosurgery: effect on cervical mucus characteristics

Eighteen women with cervical ectropion and 12 women with ectropion and vaginal discharge were treated by cryosurgery. Evaluation of the cervical mucus characteristics by cervical score and in vitro penetration test was performed before treatment and 2 months later. In the group with ectropion only (group A) the total cervical score was 5.7 +/- 0.4 and 11.9 +/- 0.06 (P less than 0.001) (mean +/- standard error) before treatment and 2 months later, respectively. In the group with ectropion and vaginal discharge (group B) the total cervical score before and after cryosurgery was 3.8 +/- 0.4 and 11.8 +/- 0.1 (P less than 0.001), respectively. In vitro penetration tests in group A before and after treatment were 0.72 +/- 0.1 and 2.9 +/- 0.08 (P less than 0.001), respectively. In group B, in vitro penetration tests before and after cryosurgery were 0.25 +/- 0.1 and 2.8 +/- 0.1 (P less than 0.001), respectively. It appears that cryosurgery improves the cervical mucus characteristics. It is recommended that infertile patients with hostile cervical mucus and ectropion will be treated by cryosurgery.     

Human papillomavirus in paired normal and abnormal cervical biopsies--implications for treatment

A total of 143 consecutive patients with abnormal cervical cytology was examined at a large colposcopy clinic in Glasgow. Each patient had paired biopsies from normal and abnormal cervical epithelium examined both histologically and by immunoperoxidase staining for human papillomavirus (HPV) infection. More than 71% of the abnormal biopsies and 39% of the normal paired biopsies had histological evidence of HPV infection. Cytological evidence of HPV infection was seen in 38.5% of cervical smears. Immunocytochemistry revealed HPV antigen in 22% of the abnormal biopsies and in 4.2% of the 'normal' biopsies. The presence of HPV infection in colposcopically normal cervical tissue both inside and outside the transformation zone may help to explain why current methods for treatment of cervical HPV infection are often unsuccessful.     

Doppler ultrasound studies of the uterine arteries in spontaneous and IVF stimulated ovarian cycles

The changes of uterine artery blood flow in women were studied throughout normal and in vitro fertilization (IVF) stimulated cycles. The obtained data showed that uterine blood flow variations are correlated to spontaneous or induced hormonal changes. Furthermore, Doppler investigation may be very important in predicting the pregnant state at a very early stage in patients enrolled in an IVF program.     

Semen pH in patients with normal versus abnormal sperm characteristics

OBJECTIVE: The World Health Organization laboratory manual, last revised in 1992, states that the normal pH of semen ranges from 7.2 to 8.0. Our experience has been that values in our patient population are consistently higher than this range. To confirm this we reviewed >1100 semen records.Study Design: All patient records from January 1994 to December 1998 that had semen pH measurements and sperm concentration and motility measurements recorded were included in this study. We also determined the semen pH in a subgroup of patients who underwent sperm preparations for intrauterine inseminations that resulted in documented pregnancies. Histograms were used to describe the populations and the Mann-Whitney test was used for group comparisons. RESULTS: For all patients (N = 1199) mean (+/-SD) semen pH was 8.2 +/- 0.3. The range was 7.3 to 9.5, with pH <8.0 in 32% of the samples. The semen pH among the patients with normal sperm concentration and motility values (n = 602) was not different from that among those with abnormal parameters (n = 597). Mean semen pH value was 8.2 for both groups. In a small group of patients (n = 19) whose sperm preparations had been documented to result in a clinical pregnancy after intrauterine insemination the semen pH was 8.3 +/- 0.3, with a range of 7.9 to 8.7. CONCLUSION: Our study questions the reference range defined by the World Health Organization for semen pH of 7.2 to 8.0. The mean values that we observed in our population, including those of samples from patients with normal sperm parameters, consistently lay outside that range.     

Measurement of breast volume by ultrasound during normal menstrual cycles and with oral contraceptive use

The volume of the human breast was measured by ultrasonographic methods with good reliability and reproducibility. Variations in breast volume of up to 36% were encountered with weekly measurements during the course of seven normal menstrual cycles. Oral contraceptives containing 35 to 50 micrograms ethynyl estradiol and amounts of norethindrone varying over a range of 0.4 to 2.5 mg/day and used for six cycles did not produce dose-related changes in breast volume as compared with untreated control subjects, but the sensitivity of the experiment was reduced by notable individual variation and relatively small sample sizes.     

Prediction of endometriosis by transvaginal ultrasound in reproductive-age women with normal ovarian size

ObjectiveTo predict endometriosis by transvaginal ultrasound (TVS) in reproductive-age women with normal ovarian size.DesignProspective study.SettingEl-Shatby Maternity Hospital, Alexandria University.Patients125 Women with symptoms suggestive of endometriosis and with normal ovarian size during TVS.InterventionsPatients were subjected to high frequency ultrasound and evaluated for the presence of ultrasound signs of endometriosis (TVS-based soft markers). All patients had laparoscopy (gold standard) immediately after TVS for documentation of the presence of endometriosis.Main outcome measuresSensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of TVS and of the TVS-based soft markers in diagnosing endometriosis.ResultsEndometriosis was confirmed laparoscopicaly in 68/125 patients (54.4%). The sensitivity, specificity, PPV, NPV and diagnostic accuracy of TVS in diagnosing endometriosis were 85.3%, 80.7%, 84.1%, 82.1% and 83.2%, respectively. Six TVS-based soft markers showed significant association (P < 0.05) with endometriosis (ovaries not at the same level, high left ovary, ovarian fixation to uterus, tender ultrasound, ovarian fixation to iliac vessels and non visualization of left ovary) with sensitivities of 85.3%, 80.9%, 80.9%, 66.2%, 55.9% and 55.9%, respectively. These markers could be considered as positive soft markers to predict endometriosis. The addition of these soft markers could improve the sensitivity, specificity, PPV, NPV and diagnostic accuracy to 97.3%, 98.5%, 95.7%, 89.9% and 91.2%, respectively.ConclusionTVS appears to be a useful imaging method for the prediction of endometriosis. The inclusion of TVS-based positive soft markers either alone or in combination improves our ability to predict endometriosis.     

Second-trimester cervical ultrasound: associations with increased risk for recurrent early spontaneous delivery

OBJECTIVE: To determine whether short cervical length or internal os funneling before 20 weeks' gestation predicts early preterm birth or pregnancy loss in women with at least one prior spontaneous early preterm birth. METHODS: Transvaginal cervical ultrasound examinations were done every 2 weeks on 69 women with singleton gestations and histories of at least one prior spontaneous birth between 16 and 30 weeks' gestation. The results of those examinations were correlated with gestational age at delivery. RESULTS: Among 53 women who had ultrasound examinations before 20 weeks' gestation, those with cervical lengths at or below the tenth percentile for the study population (22 mm, n = 4) or funneling of the internal os (n = 5) were more likely than women without those factors to have spontaneous preterm births within 2 weeks (33% versus 0%, P = .01) or 4 weeks from the ultrasound examination (67% versus 0%, P < .001) or before 35 weeks' gestation (100% versus 19%, P < .001). Short cervical length or funneling between 20-24 and 25-29 weeks was also associated with increased risk of spontaneous preterm birth before 35 weeks' gestation (P < or = .05 and P = .002, respectively) but not with increased risk of spontaneous preterm birth within 2 or 4 weeks of ultrasound examination. CONCLUSION: Women with prior early spontaneous preterm births who have short cervical lengths or funneling of the internal cervical os before 20 weeks' gestation are at increased risk of subsequent spontaneous preterm birth.     

Human papillomavirus in paired normal and abnormal cervical biopsies–implications for treatment

Summary. A total of 143 consecutive patients with abnormal cervical cytology was examined at a large colposcopy clinic in Glasgow. Each patient had paired biopsies from normal and abnormal cervical epithelium examined both histologically and by immunoperoxidase staining for human papillomavirus (HPV) infection. More than 71% of the abnormal biopsies and 39% of the normal paired biopsies had histological evidence of HPV infection. Cytological evidence of HPV infection was seen in 38.5% of cervical smears. Immunocytochemistry revealed HPV antigen in 22% of the abnormal biopsies and in 4.2% of the 'normal' biopsies. The presence of HPV infection in colposcopically normal cervical tissue both inside and outside the transformation zone may help to explain why current methods for treatment of cervical HPV infection are often unsuccessful.     

Management of women with abnormal cervical cytology: treatment patterns and associated costs in England and Wales

OBJECTIVE: To evaluate the time from abnormal Papanicolaou smear detected during routine screening to the initiation of investigation and treatment of subjects and to evaluate its related costs. DESIGN: Retrospective study of clinical records from women with abnormal cervical smears. SETTING: Six specialist gynaecology/colposcopy clinics in England and Wales. SAMPLE: Six hundred subsequent women (100 per clinic) with first abnormal cervical smear result at the specialist gynaecology/colposcopy clinic. METHODS: Details of all clinic visits, tests and procedures during 24 months starting from the first abnormal cervical smear were collected from the year 2002. MAIN OUTCOME MEASURES: Patterns of management after initial abnormal smear, time to start the investigation and/or treatment expressed in days/months and treatment costs by cytology and histology grades. RESULTS: Significant age differences were observed between women with early grades of precancer lesions (32 years) and cancer (49 years) (P < 0.05). Subgroup analysis of women younger than 26 years indicates a representation of this age group in all the histology grades including cancer. Median time to initiate the investigation and/or treatment was 50 days. In contrast, for 5% of women, delay in management lasted for >1 year. Colposcopy and repeated cervical smears were the most frequent systematic investigations performed, while the large loop excision of the transformation zone procedure was the principal therapeutic procedure. Analysis of average treatment costs by referral cytology showed small differences between the three grades of cytological diagnoses (mild dyskaryosis, 408.96 British pound; moderate dyskaryosis, 442.55 British pound and severe dyskaryosis, 493.74 British pound). Analysis by histology grade showed that the cost for women with a negative result (263.34 British pound) differed markedly from that for women with cervical intraepithelial neoplasia (CIN) (CIN1, 419.39 British pound; CIN2, 572.29 British pound; and CIN3, 584.92 British pound). CONCLUSION: Time to investigation could be improved for a subgroup of women. Costs associated with investigation and treatment of women with abnormal cervical smears differ significantly between analyses by cytology and histology grade. This needs to be borne in mind when designing cost-effectiveness studies of cervical screening.     

Intrapartum vibroacoustic stimulation in cases of normal and abnormal fetal heart rate patterns

The fetal heart rate (FHR) response to a vibroacoustic stimulation was studied in 100 women during active labor. Three types of FHR responses were noted: acceleration, tachycardia of duration longer than 2 min, and combined acceleration-deceleration response. The last type was significantly more common in labors with abnormal FHR tracings. All fetuses demonstrating FHR response to the stimulation, including those with abnormal FHR tracings, had good outcome. The vibroacoustic stimulation is easily performed, noninvasive, and has no contraindications. Its possible application as an intrapartum test of fetal well-being awaits further clinical confirmation.