[Interest of a geostatistical approach to analyze the geographical disparities in human papillomavirus vaccine coverage in France]. / Intérêt d'une approche géostatistique pour analyser les disparités géographiques de la couverture vaccinale contre les papillomavirus humains en France.

BACKGROUND: The use of geostatistical methods remains rare in health studies. In order to assess the usefulness of the geostatistical approach in epidemiology, we chose to apply these methods to the vaccination coverage rate (VCR) against human papillomavirus (HPV) in France. Indeed, HPV vaccine coverage remains low in France and geographical disparities are sizable. The objective of this study was to identify the socioecological factors that may explain these geographical variations. METHODS: Sociological, economic and behavioral data for 2016 have been gathered (demographics and public health database, web and social networks) and were correlated with the HPV VCR vaccine coverage over the French territory. Homogeneous geographical areas defined by strong correlations for groups of variables were selected. In each homogeneous area, principal component analysis was performed and a geostatistical approach provided an estimate predicting vaccine coverage at a given scale. RESULTS: HPV VCR spatial variations in France cannot be fully explained by a single model. In urban areas, a low rate of HPV VCR is preferentially associated with unfavorable socioeconomic factors (poverty, unemployment, immigration). In rural areas, HPV VCR is preferentially associated with sociocultural factors (socio-professional categories, education level, interest in alternative medicines the anti-vaccine movement). Two secondary geographical areas were defined: the Île-de-France region and 12 departments in northeastern France. In the Île-de-France region, the association with the economic factors one again appears as in urban areas in general. The northeasteran departments represent a particular case insofar as HPV VCR is relatively high, notwithstanding economic poverty indicators. CONCLUSION: Geostatistical modeling successfully identifies new potential explanations for HPV VCR geographical disparities in France. These results could help to adapt or develop future vaccination programs in specific areas by taking into account the sociological, economic and behavioral characteristics of their populations.

Human Papillomavirus (HPV) vaccination coverage among French adolescents: A claims data study.

BACKGROUND: The French cancer control strategy 2021-2030 aims to achieve 80 % human papillomavirus (HPV) vaccination coverage. Since 2021, HPV vaccination is also recommended for boys aged 11-14 years, with a catch-up vaccination recommended for unvaccinated adolescents aged ≤19 years. The PAPILLON study used claims data to monitor the evolution of HPV Vaccination Coverage Rate (VCR) in the French population. METHODS: The annual HPV VCR was described from 2017 to 2022. Partial vaccination was defined as the dispensing of at least one dose of HPV vaccination. Full scheme vaccination was defined according to the current French recommendations as two or three doses of HPV vaccine over an 18-month period. Annual HPV vaccine initiation rates were estimated on 11-14 and 15-19-year-olds adolescents. Cumulative VCR were estimated on adolescents aged between 11 and 19 years at the time of first vaccination. RESULTS: Overall, 1,773,900 females and 592,167 males initiated HPV vaccination between 2017 and 2022. Initiations occurred between 11 and 14 years for 67.3 % of females and 62.4 % of males with a median time between the first two doses of 195 days and 190 days, respectively. In girls, the cumulative vaccination rate for the partial scheme vaccination at 15 y.o. increased from 28.1 % in 2017 to 50.9 % in 2022. Similarly, the cumulative vaccination rate for the full scheme vaccination at 16 y.o. increased from 15.5 % in 2017 to 33.8 % in 2022. In 2022, the initiation rates for males were 12.6 % at age 14 and 1.9 % at age 19. CONCLUSIONS: HPV vaccination coverage increased between 2017 and 2022 among girls targeted by the recommendation but remains insufficient. The results of this study show a tentative but promising start to vaccination in boys. This study will monitor the effects of actions taken to improve vaccination, including the extension of vaccination competencies to community pharmacists since end of 2022.

[Outpatient laparoscopic hysterectomy in France: A monocentric randomized trial]. / Hystérectomie cœlioscopique ambulatoire en France : étude randomisée unicentrique.

OBJECTIVE: To demonstrate the feasibility of outpatient laparoscopic hysterectomy using the assessment of post-operative quality of life. METHODS: A prospective randomized single-center trial was performed in France between 2013 and 2016. A total of 42 patients needed laparoscopic hysterectomy was included. Postoperative quality of life was assessed using the standardized Euroquol questionnaire. Patients filled the score before the operation and then on the 3rd and 30th postoperative day. Secondary outcomes were assessment of postoperative pain, overall quality of life, analgesic use, and anxiety. The patients were randomized into two groups, group A with a conventional hospital stay of 2 to 3 days and group B with a short stay and a discharge the day after the intervention. RESULTS: Twenty-one patients were randomized to group A as well as group B. We did not find any significant differences between the two groups in our study either on our primary outcome or in the seconds ones. On day 3, the average of Euroquol score was 0.68 for group A against 0.50 for group B (P=0.05). Likewise, the scores for postoperative pain were similar with 70.6 in group A and 61.8 in group B (P=0.21). The trend was the same for quality of life score or anxiety. CONCLUSION: Our study shows the possibility and the safety of outpatient laparoscopic hysterectomy.

A prospective randomized study of two reminding strategies: telephone versus mail in the screening of cervical cancer in women who did not initially respond.

OBJECTIVE: To compare the efficacy and cost-effectiveness of two reminding strategies addressed to women who did not respond to a first invitation to undergo cervical cancer screening. STUDY DESIGN: A randomized study was carried out by a programme created in Alsace to organize cervical cancer screening. In total, 10,662 women who did not have a smear test 1 year after a first notice was sent, were randomly allocated to receive either a new letter with a reply coupon or a telephone call. The uptake of screening was measured using routine data. Efficacy and direct costs of the two methods were compared. RESULTS: Uptake at 8 months was 6.3% [95% confidence interval (CI) 5.6-7.0%] for telephone calls and 5.8% (95% CI 5.2-6.4%) for letters. The difference was not significant. More information was collected through telephone calls than by letters, but with less reliability. Furthermore, telephone calls were more costly. CONCLUSIONS: We found that in our region, a mail reminder was as effective as, and less expensive than, a telephone call; moreover, it was applicable to the whole population, including patients without a telephone.

European guidelines for clinical management of abnormal cervical cytology, part 2.

The current paper presents the second part of chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. The first part of the same chapter was published in a previous issue (Cytopathology 2008;19:342-54). This part provides guidance on how to manage and treat women with histologically confirmed cervical intraepithelial neoplasia. The paper describes the characteristics, indications and possible complications of excisional and ablative treatment methods. The three options to monitor the outcome after treatment (repeat cytology, HPV testing and colposcopy) are discussed. Specific recommendations for particular clinical situations are provided: pregnancy, immuno-suppression, HIV infection, post-menopause, adolescence and cyto-colpo-histological disparity. The paper ends with recommendations for quality assurance in patient management and some general advice on how to communicate screening, diagnosis and treatment results to the woman concerned. Finally, a data collection form is attached.

[Use of HPV virologic test for atypical glandular cells in Alsace between 2014 and 2016]. / Recours au test virologique HPV dans la prise en charge des atypies glandulaires en Alsace entre 2014 et 2016.

OBJECTIVES: The new recommendations by the National Institute of Cancer (January 2017) recommend the use of a complementary human papillomavirus (HPV) virologic test during the diagnosis of atypical glandular cells in pap smear. The aim of this study was the performance analysis of the HPV virologic test for the detection of significant histological cervical abnormalities (CIN2 or more) in case of atypical glandular cells before the new recommendations were published. METHODS: We performed a descriptive and retrospective cohort study in Alsace between January 2014 and December 2016. We have included, from the EVE-association database, the patients with atypical glandular cells in pap smear. RESULTS: In total, 1074 patients had a pap smear with atypical glandular cells ; 0.18% of total pap smears. This study included 152 patients who had a HPV test. We observed 6 cases of CIN2 (3.9%) and 12 cases of CIN3 (7.9%). No in situ adenocarcinoma nor invasive carcinoma were detected. The sensitivity of the HPV test was 88.9% (95% CI: [0.65; 0.99]), the specificity was 65.9% (95% CI: [0.55; 0.76]), the positive predictive value was 34% (95% CI: [0.21; 0.49]) and the negative predictive value was 96.8% (95% CI: [0.89; 0.99]). CONCLUSION: The detection of HPV in atypical glandular cells seems to be powerful with an excellent negative predictive value but, because of moderate sensitivity and due to the risk of histologic lesion progression, the current recommendations should to be applied with care.

European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1.

The current paper presents the first part of Chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to manage women with abnormal cervical cytology. Throughout this article the Bethesda system is used for cervical cytology terminology, as the European guidelines have recommended that all systems should at least be translated into that terminology while cervical intraepithelial neoplasia (CIN) is used for histological biopsies (Cytopathology 2007; 18:213-9). A woman with a high-grade cytological lesion, a repeated low-grade lesion or with an equivocal cytology result and a positive human papillomavirus (HPV) test should be referred for colposcopy. The role of the colposcopist is to identify the source of the abnormal cells and to make an informed decision as to whether or not any treatment is required. If a patient requires treatment the colposcopist will decide which is the most appropriate method of treatment for each individual woman. The colposcopist should also organize appropriate follow-up for each woman seen. Reflex testing for high-risk HPV types of women with atypical squamous cells (ASC) of undetermined significance with referral for colposcopy of women who test positive is a first option. Repeat cytology is a second possibility. Direct referral to a gynaecologist should be restricted to special circumstances. Follow-up of low-grade squamous intraepithelial lesion is more difficult because currently there is no evidence to support any method of management as being optimal; repeat cytology and colposcopy are options, but HPV testing is not sufficiently selective, unless for older women. Women with high-grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot exclude HSIL (ASC-H) should be referred without triage. Women with glandular lesions require particular attention. In a subsequent issue of Cytopathology, the second part of Chapter 6 will be presented, with recommendations for management and treatment of histologically confirmed intraepithelial neoplasia and guidance for follow-up of special cases such as women who are pregnant, postmenopausal or immunocompromised.

Laparoscopic pelvic lymphadenectomy in patients with intermediate-risk endometrial cancer: Is it worth it?

OBJECTIVE: The main aim of this study is to evaluate operative and postoperative morbidity of laparoscopic pelvic lymphadenectomy as well as its potential impact on the postoperative management in patients with an intermediate-risk of endometrial cancer. METHODS: We did a retrospective study between January 2009 and December 2013. We included all patients operated by laparoscopy for endometrial cancer presumed to have an intermediate-risk of recurrence. Pelvic lymphadenectomy in this group of patients was performed at the discretion of operating surgeons. Patients were consequently divided into two groups according to whether or not pelvic lymphadenectomy was performed. We made a comparative analysis between these two groups. RESULTS: Overall, 116 patients were managed for endometrial cancer presumed to be intermediate-risk. Among these, 93 received treatment with laparoscopy and were included in the study. Patients' characteristics did not differ between the two groups. The mean duration of surgery was significantly longer when pelvic lymphadenectomy was performed. The average number of retrieved lymph nodes was 13 and we had seven patients with positive lymph nodes (10%). CONCLUSION: Pelvic lymphadenectomy allows a better postoperative classification for some patients without more complication.

[Imiquimod and immune response modifiers in gynaecology]. / Imiquimod et autres immunomodulateurs en gynécologie.

Immunomodulators have been used for some time in various medical specialities, but have only recently been used in gynaecology. The first drug in this therapeutic class, Immiquimod (Aldara), has been shown to be effective in treating lesions induced by Human Papillomavirus (HPV) such as genital warts or cervical and vulvar dysplasia, by stimulating the immune system of an infected individual. Thanks to its ease of use and its few side effects, Imiquimod would appear to be, in the future, the treatment of choice for these types of viral infections, alone or in association with therapeutic vaccines or physical abative therapies as a prevention of relapses. This review aims at summarizing and clarifying the mechanism of action of the different immunomodulators, their indications and their effectiveness in gynecologic practice.

[Left colon necrosis after endoscopic para-aortic lymph node exploration in a cervical carcinoma stage IIB]. / Nécrose colique gauche après un curage lomboaortique coelioscopique pour cancer du col utérin de stade IIB.

Authors report a left colon ischemia six days after laparoscopic para-aortic lymphadenectomy in the staging of advanced cervical carcinoma. Before surgery, positron emission tomography scanning was performed: there were no para-aortic nodal metastasis. The histologic examination confirmed the radiological staging. Positron emission tomography scanning could avoid surgery in the case of patients with high risks morbidity factors.

[Health-related quality of life in patients treated for ovarian cancer: tools and issues]. / Étude de la qualité de vie dans les néoplasies ovariennes : outils et enjeux.

Health-related quality of life (QoL) in patients treated for ovarian cancer is directly and heavily impacted by the natural history of cancer, its evolution and its therapeutic modalities. The evaluation and consideration of various parameters of QoL seems to be a major issue. Indeed, on the one hand, it is essential to take into account the opinion of patients in the choice of therapeutic strategies for this cancer with a poor prognosis and, on the other hand, more and more studies show that QoL is an independent prognostic factor in ovarian cancer. Improvement in this case, in addition to being an endpoint by itself, would potentially improve the overall survival of patients. To date there are several tools to assess QOL of patients with ovarian cancer. The 2 questionnaires most commonly used are: FACT-O and the EORTC QLQ-OV28. The aim of our study was to evaluate from a review of the literature, the reciprocal effects of ovarian cancer on QoL and QoL on ovarian cancer survival, as well as specificities of each of the 2 questionnaires most commonly used in assessing the QoL.

[Reliability of endocervical curettage after conservative treatment of intraepithelial neoplasia of the cervix]. / Fiabilité du curetage endocervical après traitement conservateur des néoplasies intraépithéliales du col utérin.

OBJECTIVE: To evaluate the reliability of endocervical curettage (ECC) in patients previously treated for CIN. PATIENTS AND METHODS: Retrospective analysis of data from 85 patients between January 1985 and December 2011 who received an ECC during monitoring after treatment of CIN. The reliability of the ECC was evaluated by comparison with the final histological analysis of the surgical specimen or the data for subsequent cyto-colpo-histological follow-up. RESULTS: Patients were referred to colposcopy either within the immediate post-treatment monitoring (n=42), meanly 9.7±5.3 months after treatment, or if cytological abnormalities were detected during long-term monitoring, meanly 78.6±52.4 months after treatment. Colposcopy was unsatisfactory in 75.3% of patients and normal colposcopic findings were found in 80% of patients. A perfect agreement between the ECC and the endocervical final diagnosis was noted in 68 patients (80%). For the diagnosis of severe cervical lesions (CIN 2+) ECC had a sensitivity of 86.2% (68.3-96.1), a specificity of 94.6% (85.1-98.9) and positive and negative predictive values of 61.4% (47.6-74.0) and 93% (83.0-98.1), respectively. CONCLUSION: The high sensitivity and negative predictive value of ECC for the diagnosis of severe post-therapeutic endocervical lesions avoid iterative treatment without increasing the risk of progression of a lesion to cancer.

Risk of cervical stenosis after large loop excision or laser conization.

OBJECTIVE: To assess the frequency of cervical stenosis in patients treated by laser conization or the loop electrosurgical excision procedure and to determine the preoperative and therapeutic factors associated with its occurrence. METHODS: Two hundred fifty-five women treated by laser conization and 277 treated by loop electrosurgical excision procedure were followed regularly by postoperative colposcopy for mean periods of 38 and 16 months, respectively. Stenosis was defined as cervical narrowing that prevented insertion of a 2.5-mm Hegar dilator. RESULTS: Thirty-eight cases of cervical stenosis, of which seven were complete, were diagnosed up to 28 months after treatment. The risk of postoperative cervical stenosis was higher for patients over 50 years of age (relative risk [RR] 3.07, 95% confidence interval [95% CI] 1.30, 7.26; P = .031), for those with a totally endocervical lesion (RR 3.79, 95% CI 1.88, 7.62; P = .001), for those with an excision 20 mm high or greater (RR 2.96, 95% CI 1.63, 5.38; P = .005), and for those with laser conization (RR 2.35, 95% CI 1.24, 4.46; P = .009). Parity, menopause, previous treatment for cervical intraepithelial neoplasia, satisfactory colposcopy, size of the lesion, its histologic diagnosis, and the extent of excision did not increase the risk for cervical stenosis. Excision was not as high with loop electrosurgical excision as with laser conization (14.3 +/- 5.0 mm versus 20.2 +/- 6.0 mm). The height of excision (RR 1.95, 95% CI 1.02, 3.76; P = .04) and a totally endocervical lesion (RR 5.07, 95% CI 1.96, 14.44; P = .001) were the only independent factors associated with postoperative stenosis identified by a multivariate analysis using logistic regression. CONCLUSION: The height of excision and a totally endocervical lesion were the main factors associated with cervical stenosis. The decreased risk associated with the loop electrosurgical excision procedure seems to be due to a shorter endocervical excision.

Cytology and colposcopy after loop electrosurgical excision: implications for follow-up.

OBJECTIVE: To analyze risk factors associated with residual and recurrent lesions after loop electrosurgical excision procedure and to assess the reliability of cytology and colposcopy in detection of these lesions. METHODS: Cytology and colposcopy were used to follow up 288 women after treatment by loop electrosurgical excision 3-6 months, 9-15 months, and 24-36 months after the procedure. RESULTS: The mean (+/-standard deviation) postoperative follow-up was 39+/-13 months (range 24-68 months). Treatment failure, defined as the persistence or recurrence of a cervical lesion, was observed in 20 patients (6.9%). The endocervical localization of the initial lesion (adjusted relative risk [RR] 13.7; 95% confidence interval [CI] 1.3, 150.1; P < .05) and incomplete excision (adjusted RR 9.1; 95% CI 3.0, 27.3; P < .001) were the only independent risk factors for treatment failure. In six cases, a second treatment was performed before the first cytologic and colposcopic visit because of incomplete excisions. The remaining 14 treatment failures were diagnosed by postoperative cytology and colposcopy, ten after the first visit, three after the second, and one after the third. To diagnose the treatment failures, colposcopy and cytology provided complementary information at the first (P < .001) and second postoperative visits (P < .05). Although the sensitivity of cytology was not significantly improved by the association of both methods, the latter decreased the number of residual lesions overlooked by cytology alone and contributed to the diagnosis of 95% of treatment failures in less than 2 years. CONCLUSION: The high detection rate obtained by combining cytology and colposcopy during the first 2 postoperative years may allow more leisurely follow-up schedules after that time and may reduce the consequences of subsequent loss to follow-up.

Prognostic factors in ovarian carcinoma in complete histologic remission at second-look surgery.

Prognosis of ovarian carcinoma in complete histologic remission (CHR) at second-look surgery is still controversial. In a series of 83 patients in CHR we studied retrospectively several prognostic factors (age, stage, histologic grade, histologic type, initial residual disease after surgery, CA 125 normalization period) to determine which patients present a high risk of relapsing after CHR and could be included in therapeutic protocols for consolidation treatment. Univariate analysis showed that the combination of CA 125 normalization < 8 weeks with absence of macroscopic tumoral residue after initial surgery permits the definition of a group with a very good prognosis, while for patients with CA 125 normalization period > 8 weeks and an initial macroscopic residual tumor, the prognosis is relatively poor (progression-free survival 100% vs. 47%, at 2 years P < 0.05). Using the Cox multivariate analysis, only the initial tumoral residue is of prognostic significance for progression-free survival; there is no prognostic significance for overall survival. The therapeutic strategy for ovarian cancer may be improved for patients in CHR after second-look surgery by determining those at high risk, making it possible to confine consolidation treatment trials to such a group.

Leiomyomatosis peritonealis disseminata. Report on two cases and differential diagnosis with peritoneal metastases of a low-grade stromal sarcoma of the ovary.

With the same aspect of multiple peritoneal leiomyomas, the diagnosis of typical leiomyomatosis peritonealis disseminata was established in two women aged 43 and 49, while in a third case the mature metastasis of a primary low-grade bilateral ovarian stromal sarcoma in a woman aged 63 was diagnosed.

Comparison of the risks of cytologic surveillance of women with atypical cells or low-grade abnormalities on cervical smear: review of the literature.

Minor cytological abnormalities--low-grade squamous intraepithelial lesions (LGSIL) and atypical squamous cells of undetermined significance (ASCUS)--are the most frequent abnormalities observed in smears performed in screening for cervical cancer. Surveillance through repeated smears has been proposed as an alternative to immediate colposcopy to reduce cost and avoid overloading colposcopy clinics. The aim of this review is to discuss the advantages and inconveniences of cytological surveillance of women with ASCUS or LGSIL, as reported in the literature. Cervical smears are not sufficient to establish the precise diagnosis of a lesion. In fact, the mean prevalence of normal cervices, high-grade CINs and cancers is estimated to be 58%, 7% and 0.5% for ASCUS and 34%, 27% and 0.2% for LGSIL. Cytological surveillance shows that minor cytological abnormalities regress in 28-69% of cases. In 6-9%, cytological regression masks a high-grade CIN, and a cancer may develop sooner or later in 0.30-1.12% of cases. Cancers often occur in patients temporarily lost to surveillance or in those with normal smears alternating with smears showing minor abnormalities. Strict modalities of surveillance are therefore required. The surveillance has to be carried out with smears repeated every 4-6 months for 2 years. If all smears are normal the regular screening at 3-year intervals may be resumed. On the other hand, an immediate colposcopy is recommended if a new abnormality is observed in these consecutive smears, regardless of its severity and of the time elapsed since the initial abnormality was discovered. With these recommendations in mind, cytological surveillance may slightly reduce the number of colposcopies but without reducing significantly the cost. At present, no arguments based on cost or efficacy clearly favour cytological surveillance over immediate colposcopy.

Diagnostic value of endocervical curettage during colposcopy.

A retrospective study including patients with cytology, colposcopy and endocervical curettage (ECC) was carried out to compare ECC outcomes to final diagnosis. ECC was performed in 68 cases for a discordance between cytology and colposcopy and in 85 cases because the lesion was incompletely visible. Complete concordance between ECC and final diagnosis was obtained in 123 cases. ECC overestimated diagnosis in eight cases (5 true false positives) and underestimated it in 20 cases (6 true false negatives). Among the latter, ECC failed to recognize invasion in seven cases. Sensitivity, specificity, positive and negative predictive values of ECC to diagnose high grade cervical intraepithelial neoplasia (CIN) and invasive lesions together were 84%, 97%, 95% and 90%, respectively. Outcomes to diagnose invasive lesions were 22%, 100%, 100% and 95%, respectively. ECC sensitivity to diagnose endocervical lesions is satisfactory but its sensitivity to establish the diagnosis of invasion is very low. Consequently, a conization is advisable when ECC has diagnosed an endocervical lesion, especially a high grade CIN.

Treatment strategy for pelvic actinomycosis: case report and review of the literature.

BACKGROUND: Pelvic actinomycosis is a chronic granulomatous suppurative disease caused by an anaerobic Gram positive organism Actinomyces israelii usually associated with intra-uterine devices. Pelvic actinomycosis can mimick pelvic or intra-abdominal malignancy leading to mutilating surgical exeresis. RESULTS: We present a pelvic actinomycosis secondary to long-standing intra-uterine device use in a 50-year old European woman treated by intravenous antibiotic therapy, and then by a total abdominal hysterectomy and bilateral salpingoophorectomy to free the pelvis from abscess. We point out the difficulty in diagnosis, and the importance of high-dose intravenous antibiotic therapy to reduce the very high risk for nearby pelvic structure injuries, reported in the literature, leading to post-operative morbidity.

Colposcopy and directed biopsy reliability during pregnancy: a cohort study.

The reliability of cytology, colposcopy, and directed biopsy were assessed in pregnancy and compared with that observed in a matched non-pregnant control group in order to evaluate the influence of pregnancy. One hundred and seventeen gravidas in which the final pathology could be ascertained and 234 control patients were examined by the same colposcopist. Concordance between cytology and final diagnosis was complete or within one degree of severity in 55.6% and 77.8% of patients, respectively. Unsatisfactory colposcopy was significantly less frequent in pregnant patients than in controls (12.8% vs. 23.1%, P = 0.023). In pregnant patients, colposcopy provided concordance, overestimation and underestimation of the final diagnosis in 72.6%, 17.6% and 9.8%, respectively. In the same group, the concordance between the histologic findings of directed biopsy and final diagnosis was complete or within one degree of severity in 83.7% and 95.9%, respectively. The reliability of cytology, colposcopy and directed biopsy was not related to pregnancy. These data show that the physiological changes which occur in pregnancy do not significantly alter the reliability of colposcopy and directed biopsy, if the colposcopist is aware of the peculiar difficulties and does not overreact to the accentuated patterns that may occur during pregnancy.