|Year : 2017 | Volume
| Issue : 2 | Page : 74-80
The prevalence and course of preinvasive cervical lesions during pregnancy in a Northern Nigerian Teaching Hospital
Fadimatu Bakari1, Muhammad A Abdul1, Saad A Ahmed2
1 Department of Obstetrics and Gynecology, Reproductive Health and General Gynaecology Unit, Faculty of Medicine, Ahmadu Bello University, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Pathology, Faculty of Medicine, Ahmadu Bello University, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
|Date of Web Publication||27-Apr-2017|
Department of Obstetrics and Gynaecology, Faculty of Medicine, Ahmadu Bello University, Ahmadu Bello University Teaching Hospital, Zaria
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: In spite of knowledge of the causes and prevention of cervical cancer, screening programs for cervical cancer have not yet been fully implemented in most developing countries including Nigeria. Documented data on the prevalence of preinvasive cervical lesion in pregnancy are scarce in our environment. Objectives: To determine the prevalence, risk factors, and course of preinvasive cervical lesion in pregnant women attending an antenatal clinic in Ahmadu Bello University Teaching Hospital (ABUTH) Zaria, Northern Nigeria Study Design: This was a cross-sectional longitudinal study. Setting: The study was conducted in an antenatal clinic of ABUTH Zaria. Materials and Methods: A prospective cross-sectional longitudinal analysis was carried out at an Antenatal Clinic of ABUTH Zaria, Nigeria. A total of 250 consecutive pregnant women who fulfilled the inclusion criteria and have given their consent were recruited into the study at the time of their first prenatal (booking clinic) visit for antenatal care. Data from the pregnant women were obtained using a pro forma to evaluate sociodemographic characteristics and risk factors for preinvasive disease. Conventional Papanicolaou smear was taken using the standard procedure. The cytopathologic findings of initial and postpartum Pap smear were documented in the pro forma. Prevalence, persistence, progression, and regression rates of preinvasive diseases were determined. Results: Out of the 250 pregnant women who had cervical cytology by Pap smear during the study, 15 had preinvasive cervical lesion, giving a prevalence rate of 6%; 13 (87%) were low-grade squamous intraepithelial lesion (LGSIL) while 2 (13%) were high-grade squamous intraepithelial lesion (HGSIL). Negative smears were seen in 158 women (63.2%). Inflammatory and other conditions of the cervix which are technically negative smears made up the remaining 30.8%. At postpartum follow-up of the 13 women with LGSIL, 2 (15.4%) became negative while persistence of the disease was observed in 9 (69.2%) of the cases. Two women with LGSIL were lost to follow-up. Of the two women with HGSIL, persistence of the disease was seen in one woman (50%) and regression of the disease was seen in the other woman. Risk factors that were found to be associated with preinvasive cervical lesion were age at coitarche <16 years, number of sexual partners since coitarche, and previous history of sexually transmitted infection and human immunodeficiency virus. Parity, smoking, and use of contraception were found not to be significant risk factors. Conclusion: Preinvasive lesion of the cervix is relatively common among antenatal clients in our center. Antenatal clients with HGSIL should have a repeat smear at the end of the puerperium before treatment. Routine Pap smear should be offered to all antenatal clients in our setting.
| Abstract in French|| |
Resumé: Le depistage pour le cancer de cervix dans les pays en voie de developpement demure inexsistant meme si les causes et facteurs de risques sont connue, et le Nigeria n'est pas exclu de se portrait. Les données sur la prevalences des lésions preinvasives du cervix chez les femmes enceintes sont rare au sud du sahara. Objectifs: Determiner la prevalence, facteurs de risques pour les lésions preinvasives du du cervix chez les femmes enceintes suivi en clinique de pre natalité a Ahmadu Bello Teaching Hospital(ABUTH) Zaria au Nord du Nigeria. Conception de l'etude: Ceci est une étude transversal et longitidunale faite a la clinique de pre natalité du centre hospitalier universitaire, Ahmadu Bello University Teaching Hospital Zaria. Materiels Et Methodes: Une étude transversal prospective a été faite a la clinique de prenatalité a ABUTH. Un total de 250 femmes enceintes rencontrant les critéres de l'etudes et toute volontaires on été selectionés lors de leurs premiere visite de suivie de grossesses a la clinique de pre natalité de ABUTH.les données sociodemographiques des patientes ont été obtenue en utilisant un pro format pour evaluer leurs facteur de risque. Un frottis cervical, fait selon les methodes standaron été fait, lors de la premiere visite et apres accouchement. Les données cytologiques prevalence, persistance et progression ou regression de lesion preinvasive ont été determiner. Resultats: Des 250 femmes enceintes ayant fait un frottis cervical, 15 avait une lesion preincavice du cervix,soit une prevalence de 6% ;13 (87%) été des lésions malpighienne intra-épithéliale de bas grade histologique(LIBG). Les 2 restants été des lésions malpighiennes intra épithéliales de haut grade histologique(LIHG). 158 frottis cervicaux étaient negatif soit 63.2%. Les lesions iflammatoires et autres conditions techiniquement classés comme negatif representait les 30,8%. Apres accouchement pour le suivie des 13 femmes avec une LIBG, 2 (15,4%) été devenu negatif alors que la persistance des lesions fut observé chez 9 (69.2%) des femmes. Deux femmes, avec LIBG, ne sont pas revenu apres accouchement.des deux cas de LIHG un cas fut persistant (50%) et l'autres cas eu une regression. les facteurs de risques associés aux lesion preinvasive du cervisx fut les premier rapport sexuel a moins de 16 ans,nombres de partenaire sexuel depuis le premier rapport, un historique de maladie sexuellement tramsnise et le une infection au HIV.L'accouchement, la cigarette et l'usage de contraceptif ont été trouvés comme risque non significatif. Conclusions: Les lesions preinvasive du cervix sont relativement presente a notre clinque de pre natalité. Les femmes enceintes avec un LIHG doivent avoir un frottis apres accouchement avant tout traitement. Un frottis de routine doit etre offer a toute les femmes lors de leur visite pre natale dans notre centre hospitalier.
Mots-clés: Persistance, grossesse, lésion preinvasif du cervix, progression, regression
Keywords: Persistence, pregnancy, preinvasive cervical lesion, progression, regression
|How to cite this article:|
Bakari F, Abdul MA, Ahmed SA. The prevalence and course of preinvasive cervical lesions during pregnancy in a Northern Nigerian Teaching Hospital. Ann Afr Med 2017;16:74-80
|How to cite this URL:|
Bakari F, Abdul MA, Ahmed SA. The prevalence and course of preinvasive cervical lesions during pregnancy in a Northern Nigerian Teaching Hospital. Ann Afr Med [serial online] 2017 [cited 2021 Sep 19];16:74-80. Available from: https://www.annalsafrmed.org/text.asp?2017/16/2/74/205281
| Introduction|| |
Preinvasive cervical lesions are precursor lesions for cervical carcinoma. These lesions begin with infection of the metaplastic epithelium of the transformation zone of the cervix with one or more of the high-risk types of human papillomavirus (HPV). Several risk factors have been associated with cervical intraepithelial neoplasia (CIN) and subsequent development of an invasive disease. These risk factors are known to be associated with HPV infection.
At least 1% of the population of childbearing women screened annually for cervical cancer will be diagnosed with CIN. The highest prevalence of HPV infection occurs in adolescents and young adults between the ages of 15–25 years where it is believed that more than 75% of new HPV infection occurs.
Published data on the prevalence of CIN in pregnancy in Nigeria and its neighboring countries are scarce, and documented studies done on the existence of these preinvasive lesions in pregnancy are lacking. The fear of inducing heavy bleeding, infection, and even the risk of an iatrogenic miscarriage represent the greatest concern that has significantly reduced diagnostic procedures on the pregnant cervix. A study in Zaria, Northern Nigeria, in 2000 by Ifenne et al. on the pattern of abnormal cervical smears in pregnancy and its relationship with lower genital tract infection showed the prevalence of cervical dysplasia of 2%. However, an increase in the prevalence of 4.8% was observed in a recent retrospective collaborative study over a 5-year period on nonpregnant women in Zaria.
Most cervical abnormalities in pregnancy reported in literature are detected from routine screening at the initiation of prenatal care in developed countries where such screening is offered. In the United States, about 2–3 million abnormal Pap smears are diagnosed each year and 5%–13% of these are detected in pregnant women.
In our environment, routine screening for cervical abnormalities in pregnancy is not practiced thereby making it almost impossible to know the prevalence rate of the disease in pregnancy, and cervical cancer rates have continued to remain unacceptably high. Given the increasing incidence of HPV infection and CIN in young women, the beginning of pregnancy may present a window of opportunity for all pregnant women who do not take part in cervical screening program to undergo cytological test. Papanicolaou smear at this visit is a standard care  despite evidence that this policy may not be cost effective in the developing countries. Where such screening programs are effective, there has been remarkable reduction in both morbidity and mortality from invasive cancer of the cervix.
The natural history of cervical neoplasia during pregnancy and postpartum period has been examined in several studies. Some studies revealed pregnancy as having no effect on cervical neoplasia, whereas others have reported higher regression rates of cervical neoplasia in the postpartum period compared with spontaneous regression of neoplasia for nonpregnant women., The hypothesis for the higher regression rate during pregnancy is that, in women with HPV infection, the typical hormonal pattern during pregnancy induces a viral activation that subsequently leads to increased spontaneous regression rates after delivery. Some authors also believe that traumatic cervical desquamation and stimulation of local immune factors associated with vaginal delivery play an important role in spontaneous regression of cervical dysplasia in the postpartum period.
In the current guideline of the American Society for Colposcopy and Cervical Pathology, observational management for women diagnosed with CIN in pregnancy is recommended.
Since these precursor lesions can be detected by screening and are amenable to treatment before it becomes invasive, pregnancy offers an opportunity to provide cervical cancer screening to our pregnant women who otherwise might never be screened. Pregnancy is often one of the few circumstances during which young healthy women who are not otherwise under the care of a doctor seek regular medical attention. It therefore poses an opportunity for us to provide cervical cancer screening that should not be missed.
This study aimed to determine the prevalence of preinvasive cervical lesion in pregnancy as well as to know the course of the disease through pregnancy and the postpartum period.
| Materials and Method|| |
The study was a hospital-based, cross-sectional, longitudinal study that was carried out at the Antenatal Clinic of Ahmadu Bello University Teaching Hospital (ABUTH) Zaria, Northern Nigeria, from June 2012 to April 2013. Consecutive pregnant women attending the booking clinic for their first prenatal visit were recruited for the study. The purpose and importance of the study were explained to the participants, and informed written consent was obtained. Anonymity was ensured to maintain confidentiality. Women who were previously treated for preinvasive cervical lesion in the past and women who were bleeding at the time of contact were excluded from the study. A total of 250 consecutive pregnant women who fulfilled the inclusion criteria were recruited. Data were obtained using a pro forma developed for the study to evaluate sociodemographic characteristics of the women and the risk factors for preinvasive cervical diseases. The pro forma contained the client's serial number, hospital, and telephone numbers. The risk factors for cervical preinvasive disease such as age, educational status, age at coitarche, number of sexual partners since coitarche, marital status, contraceptive use, type of family union, parity, previous history of sexually transmitted diseases, human immunodeficiency virus (HIV) status, and history of smoking and duration of smoking were also obtained.
The women were again counseled properly on the procedure to be carried out. First cervical smears were obtained at the booking visit. The participants were placed in the lithotomy position, and a sterile bivalve speculum was inserted into the vagina to expose the cervix. The cervix was visualized using an angle point lamp to identify the squamocolumnar junction of the cervix. After cleaning away excess mucus using a cotton swab, Ayres spatula was used to scrape cells from the squamocolumnar junction of the transitional zone of the cervix by rotating it through 360°. The cells were smeared on two glass slides and immediately fixed in 95% ethanol. Pathology request forms were appropriately filled stating clearly the pregnancy state of the women and their estimated gestational age. The patient's serial and telephone numbers were clearly written on the request forms to facilitate follow-up. The sample containers along with the request forms were then taken to the pathology laboratory for slide preparation. The smears were stained using the Papanicolaou staining technique. A trained cytopathologist (the third author) interpreted all the slides. The Bethesda system of classification was used in grading preinvasive cervical lesion. Repeat smears were obtained after at least 2 weeks from the initial smear in patients with cytological report of unsatisfactory and inadequate smear during pregnancy. Those women with intraepithelial neoplasia report had a repeat Pap smear at 6 weeks postpartum. The results of the investigation were recorded in the pro forma. The data were analyzed using SPSS Version 16 (IBM Inc, USA). Descriptive and summary statistics and cross-tabulation were used to describe the data in relation to relevant variable. Bivariate analysis was performed to test for association between variables. The P value was set at <0.05. Approval for the study was given by the Ethical Review Board of ABUTH, Zaria.
| Results|| |
All the 250 pregnant women who attended the booking clinic of ABUTH, Zaria, during the study period satisfied the selection criteria and were screened for preinvasive cervical cancer by Papanicolaou smear.
Majority of the women were in the age range 20–29 (52.8%) years. The sociodemographic characteristics [Table 1] of these women showed that almost half of the women, 123 (49.2%), were Hausas by tribe and the entire participants except one were married. The educational level of the women revealed that most of the women had formal education with 139 (55.6%) women having tertiary education. The minimum parity was 0 (28%) while the maximum parity was 12. Majority of the women, 222 (88.8%), had <5 deliveries. The gestational age of the participants at the time of booking ranged between 6 and 41 weeks. Most women, 145 (58%), booked in the second trimester.
[Table 2] shows the prevalence of preinvasive cervical lesion in pregnancy. The total number of pregnant women with preinvasive cervical lesion at booking which comprises both low-grade squamous intraepithelial lesion (LGSIL) and high-grade squamous intraepithelial lesion (HGSIL) was 15, while those with negative cervical smears were 235. These gave a prevalence rate of 6%.
|Table 2: Prevalence of preinvasive cervical lesion in pregnancy at booking|
Click here to view
[Table 3] shows cytopathology breakdown report at booking. The number of women with negative cervical cytology was 158 (63.2%) while those with inflammatory and other conditions made up 30.8%.
Comparison between antenatal and postnatal Pap smear was done in 13 of the 15 women with preinvasive cervical lesions who returned for postnatal follow-up at 6 weeks postpartum. As shown in [Table 4], the course of LGSIL at booking revealed that of the 13 women with LGSIL, 2 (15.4) women regressed to become negative. Nine (69.2%) women persisted as LGSIL and two women were lost to follow-up. None of the women with LGSIL progressed to HGSIL. The course of HGSIL at booking showed that of the two women with HGSIL, none of them regressed to become negative. One (50%) woman regressed to LGSIL at 6 weeks postpartum, and the other woman persisted as HGSIL at 6 weeks postpartum. [Figure 1] are histogram of the course of preinvasive disease.
|Table 4: Comparison of antenatal Pap smear with postpartum cytopathology smear|
Click here to view
The influence of sociodemographic and reproductive profile on preinvasive lesion was analyzed and the result is as shown in [Table 5].
|Table 5: Influence of sociodemographic and reproductive profile on preinvasive cervical lesion|
Click here to view
Age, ethnicity, parity, and gestational age have no influence on preinvasive cervical lesion. Low educational level influences development of preinvasive cervical lesion (P = 0.02).
[Table 6] shows influence of risk factors in the etiology of preinvasive cervical lesion.
Age at coitarche, number of sexual partners since coitarche, previous sexually transmitted infection and HIV were found to be statistically significant risk factors in the development of preinvasive cervical lesion with P< 0.05. Parity, smoking, and use of contraception were found not to be statistically significant risk factors.
| Discussion|| |
The prevalence of preinvasive cervical lesion in pregnancy in this study was 6%. This was a higher figure compared with the 2% found 12 years previously from the same center; although smaller sample size used in the previous study could be a factor for the smaller rate seen, it was relatively comparable to 4.8% in a retrospective collaborative analysis of 270 Pap smears of nonpregnant women done from the same center 2 years earlier. The incidences of CIN and HPV infection in pregnant women are generally comparable to that of nonpregnant women., In Maiduguri, Northern Nigeria, the prevalence of 7.8% was obtained following review of Pap smear over 15-year period.
A much higher prevalence of 14% in our center was however obtained in a case–control study carried out among 369 women seeking to know the cervical smear pattern in patients with chronic pelvic inflammatory disease (PID) and those without chronic PID attending gynecology and family planning clinics of ABUTH, Zaria. Higher prevalence was seen in the PID group.
From the studies cited from different geographical regions of Nigeria, it is evident that most of the studies carried out are on nonpregnant women, women with HIV, and other high-risk women. There are few studies generally on preinvasive cervical lesion in pregnancy in developing countries.
The prevalence of abnormal Pap test reported in the developed world is between 0.5%–3%, this is lower than the findings in this study of 6%, but in the former, larger population consisting of both pregnant and nonpregnant women was used.
To the best of our knowledge, there is no documented study on the course of preinvasive cervical lesion in pregnancy. Studies done on course of preinvasive cervical lesion in developed countries showed surprisingly high rate of regression from HGSIL to LGSIL and from LGSIL to negative smears during pregnancy and delivery. Progression of preinvasive disease to invasive disease during pregnancy is rare. Ahdoot et al. revealed an overall postpartum regression of HGSIL of 48%. This is similar to the regression rate in this study. Kiguchi et al. reported a regression rate of 54% within 12 weeks of delivery in 78 women with HGSIL. Traumatic cervical desquamation and stimulation of local immune factors associated with vaginal delivery were speculated to play an important role in spontaneous regression of cervical dysplasia in the postpartum period.
Studies have also observed that spontaneous regression of preinvasive cervical lesion is higher in pregnant women than in nonpregnant women. The reported spontaneous regression rate of HGSIL ranges between 6% and 13% in nonpregnant women and 30% and 54% in pregnant women. In a retrospective analysis of 51 pregnant women diagnosed with preinvasive cervical lesion by Mailath-Pokorny et al. in Vienna between 2005 and 2010, there was higher spontaneous regression rates and lower persistence rates for CIN I–III in pregnant women when compared to nonpregnant women (56.9% vs. 31.4%, P = 0.010).
Age at first sexual intercourse, increasing number of sexual partners since coitarche, previous history of sexually transmitted infection and HIV, and educational level were found to be statistically significant risk factors in the development of preinvasive cervical lesion in our pregnant women. This is however not surprising because these are factors that are interrelated and linked in that they are risk factors associated with acquisition of HPV infection. Low educational status influences the prevalence of preinvasive lesion in most developing countries where organized screening programs are lacking. Women with low or no education are likely to be ignorant and be less informed about performing routine Pap smear. On the contrary, parity, smoking, and use of contraception were found not to be statistically significant. The present study confirmed the significant association between increasing number of sexual partners and preinvasive cervical lesion as it was previously found in Maiduguri, Nigeria. The number of sexual partners is the major independent risk factor for preinvasive cervical lesion whereas age at first sexual intercourse, high parity, and low socioeconomic status are cofounders. These factors are prevalent in Nigeria and other developing countries.
| Conclusion|| |
Organizing effective screening programs in our antenatal care facility is crucial in other to detect precursor cervical lesions and eliminating death from cervical cancer in women of child-bearing age. The use of cervical cytology at the first prenatal/booking clinic followed by an appropriate treatment when necessary might be the key factor to reducing invasive cervical cancer in the developing countries as it did in the developed countries. Antenatal clients with HGSIL should be managed conservatively and have a repeat smear and colposcopically directed biopsy at 6 weeks postpartum when indicated before treatment since studies have documented higher regression rate in the postpartum period.
I would like to express my special thanks and gratitude to my supervisors Dr. MA Abdul and Dr. SA Ahmed for giving me an opportunity and insight on how to conduct this research work and provided me with all the support and guidance which made me to complete this work. I would not forget my Mentor and Head of Department Dr. AJ Randawa for his encouragement and guidance throughout my residency program. I owe my profound gratitude to the staff of Histopathology department especially Dr. Umar Muhammad, Mallam Abdullahi Muhammad, and Bello Babale who assisted me at various levels in their own capacity. Furthermore, I would like to acknowledge with much appreciation the crucial role of Dr. MS Ibrahim of Community Medicine Department, ABU, Zaria, who helped me relentlessly as a statistician with my data analysis. Special thanks go to my colleagues and friends who helped me greatly during this work. I wish to thank my spouse, parents, children, and sisters for their support and prayers. Finally, I thank Almighty Allah for giving me the knowledge, health, and strength to do this work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ellen E. Management of abnormal Pap test. In: James RS, Ronald G, Beth YK, Arthur FH, editors. Danforth's Obstetrics and Gynecology. 9th
ed. Philadephia: Lippincott Williams and Wilkins; 2003. p. 59-66.
Insinga RP, Glass AG, Rush BB. Diagnoses and outcomes in cervical cancer screening: A population-based study. Am J Obstet Gynecol 2004;191:105-13.
Dempsey AF. Human papillomavirus: The usefulness of risk factors in determining who should get vaccinated. Rev Obstet Gynecol 2008;1:122-8.
Ifenne DI, Shittu SO, Ekwempu CC. Cervical smear in pregnancy: Zaria experience. Niger J Surg Res 2001;3:81-4.
Adekunle OO, Samaila MO. Prevalence of cervical intraepithelial neoplasia in Zaria. Ann Afr Med 2010;9:194.
] [Full text]
Jones BA, Davey DD. Quality management in gynecologic cytology using interlaboratory comparison. Arch Pathol Lab Med 2000;124:672-81.
Hunter MI, Tewari K, Monk BJ. Cervical neoplasia in pregnancy, part 1: Current treatment of pre invasive disease. Am J Obstet Gynecol 2008;199:3-9.
Cunningham FG, MacDonald PC, Gant HF, Levon KJ, Gilstrap LC, editors. William Obstetrics. 19th
ed. Norwalk, Connecticut: Appleton and Lange; 1993. p. 25-7.
Carter PM, Coburn TC, Luszczak M. Cost-effectiveness of cervical cytologic examination during pregnancy. J Am Board Fam Pract 1993;6:537-45.
Hogenmiller JR, Smith ML, Stevens LC, McIntosh DG. Patterns of Pap smear screening in women diagnosed with invasive cervical cancer. J Gynecol Surg 1994;10:247-53.
Kiguchi K, Bibbo M, Hasegawa T, Kurihara S, Tsutsui F, Wied GL. Dysplasia during pregnancy: A cytologic follow-up study. J Reprod Med 1981;26:66-72.
Mailath-Pokorny M, Schwameis R, Grimm C, Reinthaller A, Polterauer S. Natural history of cervical intraepithelial neoplasia in pregnancy: Postpartum histo-pathologic outcome and review of the literature. BMC Pregnancy Childbirth 2016;16:74.
Serati M, Uccella S, Laterza RM, Salvatore S, Beretta P, Riva C, et al.
Natural history of cervical intraepithelial neoplasia during pregnancy. Acta Obstet Gynecol Scand 2008;87:1296-300.
Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al.
2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 2013;121:829-46.
Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, et al.
The 2001 Bethesda system: Terminology for reporting results of cervical cytology. JAMA 2002;287:2114-9.
Xavier-Júnior JC, Dufloth RM, do Vale DB, Tavares TA, Zeferino LC. High-grade squamous intraepithelial lesions in pregnant and non-pregnant women. Eur J Obstet Gynecol Reprod Biol 2014;175:103-6.
Stonehocker J. Cervical cancer screening in pregnancy. Obstet Gynecol Clin North Am 2013;40:269-82.
Audu BM, Elnafaty AU, Pindiga HU. Prevalence of abnormal cervical smears from sporadic screening in a gynaecologic clinic. Niger Med Pract 2007;5:114-8.
Abdul MA, Shittu SO, Randawa JA, Shehu MS. The cervical smear pattern in patients with chronic pelvic inflammatory disease. Niger J Clin Pract 2009;12:289-93.
Ahdoot D, Van Nostrand KM, Nguyen NJ, Tewari DS, Kurasaki T, DiSaia PJ, et al.
The effect of route of delivery on regression of abnormal cervical cytologic findings in the postpartum period. Am J Obstet Gynecol 1998;178:1116-20.
Audu BM, El-Nafaty AU, Khalil M, Otubu JA. Sexual attitudes and their relation to cervical intraepithelial neoplasia in Maiduguri, Nigeria. J Obstet Gynaecol 1999;19:412-6.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]