Long-term effects of surgically corrected menstrual outflow obstruction: A case-control study.

OBJECTIVE: To enhance evidence-based knowledge on long-term sequalae in patients with surgically corrected obstructing Müllerian anomalies. METHODS: This long-term case-control study included patients with menstrual outflow obstruction due to congenital anomalies of the uterus or vagina, who were at least 18 years old, and for whom 2 years had elapsed since the first surgery at the start of this study. The control group consisted of women without current gynecological problems. Patients underwent a surgical correction at the Radboud University Medical Center Nijmegen between 1980 and 2013. Of 78 patients approached, 38 (49%) were included in this study. The control group consisted of 54 females. The main outcome measures were pain and health state. The following questionnaires were used: Visual Analogue Scale pain scores, European Quality of Life-5 Dimensions questionnaire (EQ-5D-3L) and the adapted Endometriosis Health Profile questionnaire (EHP-30). RESULTS: Patients had higher actual and maximum abdominal pain scores compared with controls (11 vs 0 [P = 0.007] and 48 vs 21 [P = 0.035], respectively). Based on the EQ-5D-3L scores, patients had more pain and discomfort (P = 0.005), more mood problems (P = 0.023), and a poorer subjective health state (P = 0.002) and self-rated health state (P = 0.031). Based on the EHP-30, patients had a significant poorer self-rated health state on four out of five subscales. CONCLUSION: In this study, following surgically corrected menstrual obstruction, patients had statistically significant higher abdominal pain scores and a poorer self-rated health state compared with controls.

Added value of involving patients in the first step of multidisciplinary guideline development: a qualitative interview study among infertile patients.

BACKGROUND: Patient involvement in scoping the guideline is emphasized, but published initiatives actively involving patients are generally limited to the writing and reviewing phase. OBJECTIVE: To assess patients' added value to the scoping phase of a multidisciplinary guideline on infertility. DESIGN: Qualitative interview study. SETTING AND PARTICIPANTS: We conducted interviews among 12 infertile couples and 17 professionals. INTERVENTION: We listed and compared the couples' and professionals' key clinical issues (=care aspects that need improvement) to be addressed in the guideline according to four domains: current guidelines, professionals, patients and organization of care. MAIN OUTCOME MEASURES: Main key clinical issues suggested by more than three quarters of the infertile couples and/or at least two professionals were identified and compared. RESULTS: Overall, we identified 32 key clinical issues among infertile couples and 23 among professionals. Of the defined main key clinical issues, infertile couples mentioned eight issues that were not mentioned by the professionals. These main key clinical issues mainly concerned patient-centred (e.g. poor information provision and poor alignment of care) aspects of care on the professional and organizational domain. Both groups mentioned two main key clinical issues collectively that were interpreted differently: the lack of emotional support and respect for patients' values. CONCLUSIONS: Including patients from the first phase of the guideline development process leads to valuable additional main key clinical issues for the next step of a multidisciplinary guideline development process and broadens the scope of the guideline, particularly regarding patient-centredness and organizational issues from a patients' perspective.

Long-term results of vaginal construction with the use of Frank dilation and a peritoneal graft (Davydov procedure) in patients with Mayer-Rokitansky-Küster syndrome.

OBJECTIVE: To describe long-term outcomes after nonsurgical and surgical treatment of vaginal agenesis in a cohort of girls and women with Mayer-Rokitansky-Küster (MRK) syndrome. DESIGN: Retrospective cohort study using a standardized case record form. SETTING: University hospital. PATIENT(S): All girls and women with vaginal agenesis due to MRK syndrome, presenting during a 40-year period (1962-2012). INTERVENTION(S): Frank dilation and surgical treatment (with the use of a peritoneal graft, i.e., the Davydov method) for vaginal agenesis. MAIN OUTCOME MEASURE(S): Functional vaginal depth and complications. RESULT(S): Two hundred fifty-four women with MRK visited the department. Urinary tract anomalies were found in 72 patients (31%), and other congenital anomalies in 59 (32%) of the patients with available data. One hundred sixty women were treated for vaginal agenesis. The mean follow-up time was 90 months (range 0-560 months). Sixty-eight patients had surgical treatment for vaginal agenesis with the use of a peritoneal graft (Davydov method) and reached a functional depth of the vagina of 7.8 cm (range 1-13 cm) Surgical therapy preceded by nonsurgical Frank dilation and/or attempted sexual intercourse did not result in more functional depth of the neovagina. The formation of granulation tissue (23%) and the tendency to obliterate (12%) were the major problems when using a peritoneal graft. CONCLUSION(S): Long-term results of both Frank dilation and Davydov neovagina procedure in experienced hands were good. The use of a peritoneal graft may be regarded as a good alternative to other widely used neovagina techniques using a graft, such as split-thickness skin graft or sigmoid neovagina.

Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial.

BACKGROUND: Tubal ectopic pregnancy can be surgically treated by salpingectomy, in which the affected Fallopian tube is removed, or salpingotomy, in which the tube is preserved. Despite potentially increased risks of persistent trophoblast and repeat ectopic pregnancy, salpingotomy is often preferred over salpingectomy because the preservation of both tubes is assumed to offer favourable fertility prospects, although little evidence exists to support this assumption. We aimed to assess whether salpingotomy would improve rates of ongoing pregnancy by natural conception compared with salpingectomy. METHODS: In this open-label, multicentre, international, randomised controlled trial, women aged 18 years and older with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube were randomly assigned via a central internet-based randomisation program to receive salpingotomy or salpingectomy. The primary outcome was ongoing pregnancy by natural conception. Differences in cumulative ongoing pregnancy rates were expressed as a fecundity rate ratio with 95% CI, calculated by Cox proportional-hazards analysis with a time horizon of 36 months. Secondary outcomes were persistent trophoblast and repeat ectopic pregnancy (expressed as relative risks [RRs] with 95% CIs) and ongoing pregnancy after ovulation induction, intrauterine insemination, or IVF. The researchers who collected data for fertility outcomes were masked to the assigned intervention, but patients and the investigators who analysed the data were not. All endpoints were analysed by intention to treat. We also did a (non-prespecified) meta-analysis that included the findings from the present trial. This trial is registered, number ISRCTN37002267. FINDINGS: 446 women were randomly assigned between Sept 24, 2004, and Nov 29, 2011, with 215 allocated to salpingotomy and 231 to salpingectomy. Follow-up was discontinued on Feb 1, 2013. The cumulative ongoing pregnancy rate was 60·7% after salpingotomy and 56·2% after salpingectomy (fecundity rate ratio 1·06, 95% CI 0·81-1·38; log-rank p=0·678). Persistent trophoblast occurred more frequently in the salpingotomy group than in the salpingectomy group (14 [7%] vs 1 [<1%]; RR 15·0, 2·0-113·4). Repeat ectopic pregnancy occurred in 18 women (8%) in the salpingotomy group and 12 (5%) women in the salpingectomy group (RR 1·6, 0·8-3·3). The number of ongoing pregnancies after ovulation induction, intrauterine insemination, or IVF did not differ significantly between the groups. 43 (20%) women in the salpingotomy group were converted to salpingectomy during the initial surgery because of persistent tubal bleeding. Our meta-analysis, which included our own results and those of one other study, substantiated the results of the trial. INTERPRETATION: In women with a tubal pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy. FUNDING: Netherlands Organisation for Health Research and Development (ZonMW), Region Västra Götaland Health & Medical Care Committee.

Galactose-1-phosphate uridyl transferase deficiency is not associated with Müllerian aplasia in Dutch patients.

STUDY OBJECTIVE: To study whether a deficiency in galactose-1-phosphate uridyl transferase (GALT) activity of mothers was an explanation for the occurrence of Müllerian aplasia of their daughters. DESIGN: A case control study. SETTING: The patients were selected from the outpatient clinic of the University Medical Center Nijmegen, and compared with the general population in The Netherlands. PARTICIPANTS: Patients (n=9) diagnosed with the syndrome of Müllerian aplasia and their mothers were included. INTERVENTIONS: A questionnaire for medical and family history was taken, and a venous blood sample and urine were collected. MAIN OUTCOME MEASURES: GALT activity (in blood), galactose and galactilol (in urine) were measured. Measured values were analyzed by Student's paired t-test. RESULTS: All patients and their mothers had normal GALT activities> or =20 micromol/h/g Hb. The mean value did not differ from the mean of the normal Dutch population, which was 31.6 (SD=5.0) mumol/h/g Hb. CONCLUSION: GALT deficiency is not an explanation for Müllerian aplasia, at least in the Dutch population.

Review of the role of the plasminogen activator system and vascular endothelial growth factor in subfertility.

OBJECTIVE: To assess the importance of the plasminogen activator (PA) system and vascular endothelial growth factor (VEGF) in subfertility. DESIGN: Review. SETTING: Two university IVF centers. INTERVENTION(S): Systematic literature search (MEDLINE, Science Direct, and bibliographies of published works). RESULT(S): The PA system in the male is involved in the passage of spermatozoa precursor cells over the blood-testis barrier, the epididymal maturation of spermatozoa, the modifications of the sperm surface for capacitation, the acrosome reaction and zona pellucida attachment, and finally the facilitation of spermatozoa to move into the fallopian tubes. In the female, the PA system plays a role during ovulation in the release of the oocyte from the follicle, the facilitation of oocyte movement into the fallopian tubes, and the extracellular matrix degradation important for angiogenesis in the ovary. The function of VEGF during fertilization is largely unknown. It has been suggested that VEGF is important for the fluid and proteins in semen and fluid secretion in the female genital tract, thereby influencing sperm motility and survival. The latter could be due to an effect of VEGF on testicular microvasculature, through which an adequate microenvironment for spermatogenesis is provided. In the female, VEGF is involved in the regulation of the cyclic ovarian angiogenesis, the development and/or selection of follicles, the accumulation of follicular fluid, and corpus luteum angiogenesis. CONCLUSION(S): The role of the PA system and VEGF in reproduction most likely is of great interest. However, much of the data are derived from experimental animal studies. So far, information on the importance of these systems in humans is scarcely investigated. Therefore, further research is required to elucidate the role of the PA system and VEGF in the pathogenesis and prevention of male and female subfertility. Eventually, this will contribute to the improvement of the diagnosis of subfertility and may possibly lead to targeted therapeutic management of subfertility.

The long term outcome of feminizing genital surgery for congenital adrenal hyperplasia: anatomical, functional and cosmetic outcomes, psychosexual development, and satisfaction in adult female patients.

BACKGROUND: There are only a few reports analyzing the long term outcome of feminizing surgery in females with congenital adrenal hyperplasia (CAH). Such analysis is crucial to evaluate the treatment and to make necessary adjustments. STUDY OBJECTIVES: To evaluate the adult outcome after feminizing surgery in adult females with salt wasting CAH. DESIGN: Retrospective observational followup investigation. SETTING: Outpatient clinic of a University Medical Center, in 2002. PARTICIPANTS: Eight patients (born 1973-1983) who underwent feminizing surgery in infancy by the same procedure and the same pediatric surgeon in our center, and 19 healthy female controls (for visual analog scales). METHODS: (a) Study of patients' records (n=8); (b) Systematic evaluation of the current situation (n=6): uroflowmetry, a written questionnaire to screen for psychopathology (Youth Adult Self Report, YASR), structured gynecologic examination and a structured psychosexual interview, including scoring on visual analog scales. RESULTS: (a) The first surgery (age 0.1-3.7 yr) consisted of clitoris reduction and vaginoplasty (single-stage) in 7 patients and clitoris reduction only in one patient. The latter patient had vaginoplasty in puberty. In puberty, 6 of the 7 patients with an initial single-stage procedure required re-vaginoplasty. All 6 patients who participated in this systematic evaluation had undergone (re-) vaginoplasty in puberty; (b) 2 of the 6 patients experienced some urinary incontinence, and in one of them, the uroflowmetry result was abnormal. The YASR showed no psychopathology, except for 1 patient with a slightly elevated externalizing score. Gynecologic examination (n=5) revealed vaginal strictures in 3 patients (1 severe, 2 mild). The 2 patients without vaginal strictures had coitus regularly. In the interview, 2 patients called themselves bisexual, the other 4 heterosexual. None of the patients had homosexual contacts. Sexual developmental milestones (romantic interest, falling in love, kissing and petting, coitus) had been reached by all, except for 1 patient who did not have coitus yet. In the patient group, satisfaction with height, body hair, and external genitalia and sexual fantasies and interest, measured with visual analog scales, was not different compared to the control group, except for satisfaction with total body appearance, which was significantly lower in the patients. CONCLUSION: Despite the poor outcome of the initial single-stage surgery in infancy and the inevitable re-operation in puberty, the adult outcome in our study population seems more positive than the findings in the few previous reports, especially with respect to sexual development and activity.