Methods
A retrospective, cross-sectional, chart review of Pap smear data was performed for all women presenting with subfertility at the Reproductive Medicine Unit (RMU), Women’s Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia, during the 14-month interval from January 2008 through February 2009. A total of 493 women attended the clinic during that interval. Routine cervical smear is offered to all patients as part of their subfertility workup. Liquid-based preparation is used to acquire the samples, which are analyzed in the pathology department according to the revised Bethesda system (2001). The samples are sent to the hospital laboratory as a routine procedure and are read by different pathologists according to the lab protocol. Data acquired from the medical records included Pap smear results, patient age, duration and description of subfertility, medical and surgical history, and complaints (if any) at the time of the initial presentation.
Results
A cervical smear was taken from 241 of the 493 patients (48.9%); the rest of the patients were not willing to undergo screening. The 241 patients who had cervical smears taken had a mean age of 30.1 years (standard deviation, 5.6 years; range 18-43 years). One hundred forty-nine (61.8%) had primary subfertility, while 92 (38.2%) had secondary subfertility. Major causes of subfertility were female factor in 97 (40.2%), male factor in 84 (35%), combined male and female causes for 23 (9.5%), and unexplained subfertility in 37 (15.3 %) couples ( Table 1 ). None of the patients had other complaints at the time of initial presentation; all patients denied tobacco use and all were HIV negative.
Causes of subfertility in study population (n=241).
Cervical cytology was normal for 166 (68.9%) patients and abnormal for 71 (29.5%); samples from 4 (1.7%) patients were unsatisfactory for evaluation. Abnormalities included epithelial cell abnormality in 7 (2.9%), inflammation in 55 (22.8%), and infection in 9 (3.7%) patients. Epithelial cell abnormalities included three atypical squamous cells of undetermined significance (ASC-US), one atypical squamous cells of high grade (ASC-H), two low-grade squamous intraepithelial lesions (LSIL), and one glandular cell abnormality (AGS) ( Table 2 ).
Epithelial cell abnormalities in patients with subfertility.
Repeated after 2 months.
All patients with abnormal results were managed according to the type of abnormality present. One patient had bacterial vaginosis and was treated with metronidazole. Other patients had candidiasis and were treated with 100 mg clotrimazole for 6 days. Repeat cultures for patients were negative. All patients with epithelial cell abnormalities were referred for colposcopy and managed according to standard practices. Repeat smears for three patients were negative within 6 months of the initial smear, and the other four women are being managed according to standard practice.
Discussion
Screening with Pap smear allows earlier detection of cervical cell abnormalities and prompts action according to set guidelines. Screening has been shown to be accompanied by a dramatic reduction in the incidence of invasive cervical cancer. 1 Unfortunately, fewer than 50% of our patients accepted the offer of routine screening for cervical assessment, which may reflect lack of public awareness of cervical cancer and the related morbidity and mortality. The 29.5% prevalence of abnormal cervical cytology in women eligible for in vitro fertilization (IVF) treatment in our clinic is surprisingly more than that reported by both van Hamont et al 15 and Lundqvist et al, 16 who found that abnormal cervical cytology was more prevalent in subfertile women than in healthy controls, with 6.1% of 699 women undergoing IVF showing this abnormality as compared with 3.9% of 77 055 matched controls. 15 – 16 The Dutch CISOE-A classification of cervical cytology was used in the van Hamont study; 15 this classification discriminates between normal cytology, borderline nuclear changes, mild dyskaryosis, moderate dyskaryosis, severe dyskaryosis, carcinoma in situ, and carcinoma of the cervix. In another case-control study, 214 women who were having IVF were compared with 197 healthy control women; the prevalence of abnormal cervical cytology in the subfertile women was 2.3%, which is also much less than the 29.5% found in our study. The authors used the CIN (cervical intraepithelial neoplasia) classification system for reporting the Pap smear results; 17 in contrast to the results of van Hamont et al, the rate of abnormal cervical cytology of 4.1% in the control group in this study was higher than that in women undergoing IVF, but it was still much less than that in our group. 16
Our study adds to the information from the few reports that address patterns of abnormal cervical cytology among subfertile women. Our evidence would have been stronger and more credible if we had compared the prevalence of abnormal cervical cytology among subfertile women to that in similarly matched fertile controls. Larger studies are needed that compare subfertile women with a control group to elicit the prevalence of abnormal Pap smear in these two populations. Additionally, screening for HPV should be done in women with epithelial cell abnormalities to help identify this potential etiological agent.
In conclusion, the high prevalence of abnormal cervical cytology in our group of subfertile women stresses the need for cervical cytology screening in patients eligible for IVF. This calls for a well-organized screening program at the national level for cervical cell abnormalities, which would allow identification of subfertile women at risk for whom early potentially life-saving measures can be undertaken. Additionally, national patient information programs are required that will create public awareness and promote understanding of the need for cervical cancer screening. At the clinic level, educational programs can include tutorials presented while women are waiting for appointments, distribution of handouts, and information displays.
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