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Biomedical subjects

W N Willemsen

Publications and source records attributed to W N Willemsen.

At least 19 recordsLinked to original sources

[Fibroids and fertility].

Fibroids are the most common benign uterine tumours. A relation between fibroids and infertility is suggested. Successful implantation depends on a normal, receptive endometrium. Fibroids can change the normal appearance of the uterine cavity and can adversely affect the endometrium. It seems that treatment of fibroids in infertility patients is useful but this is not yet proven scientifically. It is advised to refrain from extirpation of fibroids in patients with fertility problems.

Contraindications↗

Obstetric outcome of twin pregnancies after in-vitro fertilization: a matched control study in four Dutch university hospitals.

In singleton pregnancies after in-vitro fertilization (IVF), increased rates of obstetric and perinatal complications have been reported. Studies that compared IVF twin pregnancies with spontaneously conceived twins have yielded conflicting results. We compared 96 IVF twin pregnancies to 96 controls after elaborate matching. The design of our study precluded matching by zygosity. The monozygosity rate was higher in the control group and this implies that beforehand the risk for a less favourable outcome in the control group was higher than in the IVF group. However, the average birthweight of the IVF children was less than that of children in the control group (P = 0.04). This was not due to more intrauterine growth retardation in the IVF group. The mean gestational age at birth was 5 days shorter in IVF than control pregnancies, and although this difference was not significant it might explain the lower birthweight in the IVF group. The discordance rate in the IVF group was significantly increased. We found no difference in perinatal mortality and morbidity. We conclude that this study provides further evidence for a different outcome of IVF twin pregnancies in comparison with spontaneously conceived twin pregnancies.

Adult↗

Leiomyomatosis peritonealis disseminata: does malignant transformation occur? A literature review.

Leiomyomatosis peritonealis disseminata (LPD) is a rare smooth muscle tumor. In the literature more than 100 cases have been described. LPD is characterized by multiple small nodules on the peritoneal surface, mimicking a malignant process with metastases, but generally demonstrates benign histologic features. Exposure to estrogen seems to play an etiologic role. Many patients have uterine leiomyomas as well. The diagnosis of LPD is easily made on biopsy. Reduction of estrogen exposure is generally sufficient to cause regression of LPD. Surgical castration or gonadotrophin releasing hormone agonists seem good alternatives in the case of progression or recurrence of LPD. In six patients a malignant leiomyosarcoma has been described shortly after the diagnosis of LPD was made. Five of these patients did not have uterine leiomyomas or exposure to exogenous or increased endogenous estrogen. The relationship with pregnancy in the sixth patient may be coincidental. Whether malignant transformation of LPD occurs remains uncertain. Characteristics of these patients differ from those of LPD patients and may indicate a high malignant potential, necessitating a different approach.

Adult↗

Single and multiple dose pharmacokinetics and pharmacodynamics of the gonadotrophin-releasing hormone antagonist Cetrorelix in healthy female volunteers.

The gonadotrophin-releasing hormone antagonist Cetrorelix is in advanced clinical development for the control of endogenous gonadotrophin secretion during the course of a fertility programme. The aim of the present study was to investigate the pharmacokinetics and pharmacodynamics of Cetrorelix following single and multiple s.c. administration of different doses. Thirty-six healthy female volunteers received either 0.25, 0.50 or 1.00 mg Cetrorelix, in a first menstrual cycle as single dose and in a second cycle as multiple dose (daily between cycle days 3 and 16). Frequent blood samples were collected for determination of Cetrorelix, follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and progesterone concentrations. Follicular growth was measured by transvaginal ultrasonography. After single administration of each dose, maximum Cetrorelix concentrations (Cmax) were reached after 1 h, and Cmax and area under curve (AUC) increased linearly with the dose. The median terminal half-life ranged from 5 to 10 h in the three different dose groups. FSH, LH, oestradiol and progesterone concentrations were suppressed, with a nadir at 6-12 h after Cetrorelix administration. During multiple administration, Cmax and AUC also showed dose-linearity. The median terminal half-life of Cetrorelix varied between 20 and 80 h. A dose-dependent suppression of FSH, LH and oestradiol concentrations was observed during treatment. After multiple administration, ovulation was delayed for 5, 10 and 13 days in the 0.25, 0.50 and 1.00 mg dose groups, respectively. In conclusion, Cetrorelix showed linear pharmacokinetics, and effectively delayed the LH surge.

Adolescent↗

Glutathione S-transferases in human ovarian follicular fluid.

OBJECTIVE: To study the levels of glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 in human preovulatory ovarian follicular fluid (FF) and pooled granulosa and cumulus cells. DESIGN: The relation of glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 with P and 17 beta-E2 concentrations were studied. SETTING: The Department of Obstetrics and Gynecology, the Department of Gastroenterology, and the Laboratory of Endocrinology and Reproduction of the University Hospital Nijmegen in Nijmegen, the Netherlands. PATIENT(S): Infertile women participating in an IVF program. RESULT(S): Detectable amounts of glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 were found in ovarian FF and pooled cumulus and granulosa cells. Concentrations of glutathione S-transferase Alpha 1-1 were always much higher than those of glutathione S-transferase Pi 1-1. Both ovarian FF concentrations of glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 did not correlate with ovarian FF concentrations of 17 beta-E2 and P. CONCLUSION(S): The high FF concentrations of glutathione S-transferase Pi 1-1 and especially of glutathione S-transferase Alpha 1-1 suggest that these enzymes may play an important role in the detoxification processes in the follicles. The lack of correlation between follicular P and 17 beta-E2 and glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 indicates that both enzymes presumably are not present as a result of the high steroid levels.

Estradiol↗

Conditions at conception and risk of menstrual disorders.

In a case-control study, we evaluated the association of the risk of menstrual disorders with four periconceptional factors: short preceding interpregnancy interval (< 6 months), low (< or = 19 years) or high (> or = 40 years) maternal age at conception, and month of conception. We divided 919 women who had visited a fertility clinic between 1991 and 1995 into three categories: cases (with mean menstrual cycle length > or = 42 or < or = 21 days, or a variation of > or = 14 days between cycles, or amenorrhea, N = 294), controls (with cycles within a range of 25-35 days and variation < or = 7 days, N = 520), and intermediates (N = 105). A self-administrable questionnaire was mailed, asking for information about maternal reproductive history and age, and potential confounders such as smoking, exercise, and level of education. Response (77%) differed little among cases, intermediates, and controls. We found elevated risks for short pregnancy intervals [adjusted odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.04-4.02] and advanced maternal age (OR = 3.24; 95% CI = 1.27-8.30) but not for low maternal age (OR = 0.58; 95% CI = 0.11-3.14) (cases vs controls). We found similar effects for intermediates vs controls. The distribution of month of conception did not differ much from controls for both cases and intermediates. The results indicate that conception after short pregnancy intervals or at advanced maternal age increases the risk of menstrual disorders in daughters. The precise etiology is unclear, but it may lie in the quality of the oocyte at conception.

Adolescent↗

Surgical treatment of symptomatic rectosigmoid endometriosis.

OBJECTIVE: To assess the results of surgical treatment of symptomatic intestinal endometriosis. DESIGN: Retrospective study. SETTING: University hospital, The Netherlands. SUBJECTS: 14 patients in whom medical treatment had failed. INTERVENTIONS: Hysterectomy (n = 5), salpingo-oophorectomy (n = 8, bilateral in 5), posterior vaginal wall excision (n = 14), and partial resection (n = 6) or anterior wedge excision (n = 8) of the rectum. MAIN OUTCOME MEASURES: Blood loss, operating time, morbidity, and relief of symptoms. RESULTS: 9 patients became symptom free (64%), 5 of whom developed postmenopausal symptoms later on. 2 had unrelated vague abdominal symptoms and 3 more could not be assessed because they underwent in vitro fertilisation and developed stimulation-related abdominal symptoms. All were content with the operative results. CONCLUSIONS: Operations for rectosigmoid endometriosis are technically difficult with a long operating time and considerable blood loss, but they are successful in relieving symptoms when conservative treatment has failed.

Adult↗

Stapedial ankylosis in the Mayer-Rokitansky-Küster-Hauser syndrome.

We describe a 21-year-old woman with congenital unilateral conductive hearing loss and an atypical form of the Mayer-Rokitansky-Küster-Hauser syndrome. To our knowledge, this is the first reported case of this syndrome in which surgery for congenital stapedial ankylosis was successful. Besides aplasia of the vagina and uterus, the patient also had various other anomalies, such as the Klippel-Feil syndrome, Sprengel's deformity, and congenital stapedial ankylosis. Congenital hearing loss is an associated characteristic of the Mayer-Rokitansky-Küster-Hauser syndrome (10% to 20% of cases), particularly in the atypical form. Against the background of the favorable results of surgery for isolated unilateral congenital stapedial ankylosis and other unilateral congenital anomalies of the middle ear that have been described in the literature and the significant advantages of bilateral hearing, we used stapedectomy to successfully treat this case of Mayer-Rokitansky-Küster-Hauser syndrome with unilateral congenital stapedial ankylosis.

Abnormalities, Multiple↗

Hormonal serum profiles and follicular development after intramuscular and pulsatile intravenous administration of human menopausal gonadotrophin.

A study was performed to compare, in a randomized way, the effect of pulsatile intravenous (i.v.) and intramuscular (im) human menopausal gonadotrophin (hMG) administration on hormonal serum profiles and follicular development in in vitro fertilization (IVF). Fourteen IVF patients participated in the study, aged between 20 and 40 years, with a normal endocrine profile, no hormonal medication used for at least 3 months previously, no endometriosis, both ovaries present and a normal male factor. Seven patients were treated with im hMG at a daily dose of 150 IU and seven patients with pulsatile i.v. hMG at a daily dose of 112.5 IU, in both cases in combination with buserelin. Ultrasonography was performed every other day during the stimulation phase and blood samples were collected once daily up to five times a day during the entire IVF cycle. Serum concentrations of follicle-stimulating hormone, luteinizing hormone, 17 beta-oestradiol, progesterone and human chorionic gonadotrophin were determined. There were no differences in hormonal profiles between the two groups. The numbers of retrieved oocytes, fertilization rates and mean embryo quality were identical in this study, as was follicular growth. In conclusion, in the present randomized study no differences were observed in hormonal levels or follicular development after im and pulsatile i.v. hMG treatment.

Adult↗

Human leukocyte antigen typing and associated abnormalities in premature ovarian failure.

A case-controlled study was designed to assess the distribution of human leukocyte antigens (HLA) A, B, Cw, DR and DQ, and associated abnormalities in patients with premature ovarian failure (POF). A total of 37 patients in a tertiary care centre were diagnosed as having POF; all were < 37 years old. A subset was HLA-typed. The occurrence of associated diseases in patients with POF was recorded. A comparison of HLA typing was made between patients with POF and 100 organ donors from the same population. No statistically significant difference in the distribution of A, B, Cw, DR and DQ antigens was found between the study and control groups when corrected for the number of antigens tested. The commonest associated abnormality was positive autoimmune screen (43.3%). Abnormal thyroid function tests were detected in 23.3% of the patients. The observed high frequency of associated autoimmune phenomena in patients with POF points to an underlying autoimmune disorder in POF and warrants further studies to unravel the pathology of this condition.

Adult↗

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome without and with associated features: two separate entities?

A multidisciplinary study was conducted on a total of 100 women with congenital absence of vagina and uterus, the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. It was possible to analyse whether the MRKH syndrome can be considered as a single clinical entity or whether two or more syndromes lie behind the title 'the MRKH syndrome'. Complete gynaecological and laparoscopic data were available on all of the patients. The patients were divided into two groups on the basis of the laparoscopic data: a typical and an atypical form of the MRKH syndrome. We performed various diagnostic investigations to establish whether there were any associated congenital anomalies. These tests included general physical examination, radiographs of the vertebral column, the upper extremities and intravenous urography (IVU), and general otorhinolaryngological and ossicular chain examinations. Associated anomalies were most common in the group with the atypical form of the MRKH syndrome. These findings suggest that there might be two different syndromes in this patient group, namely an isolated form of congenital agenesis of the vagina and uterus and a more generalized condition, in which agenesis of the vagina and uterus is a major and perhaps even obligatory characteristic. The term MRKH syndrome should no longer be used for the atypical group. A suggestion has been made to call this type the GRES [genital (G), renal (R), ear (E), skeletal (S)] syndrome.

Abnormalities, Multiple↗

Hearing loss and the Mayer-Rokitansky-Küster-Hauser syndrome.

The hearing of 51 female patients with the Mayer-Rokitansky-Küster-Hauser syndrome was examined using otoscopy and standard audiometry. A unilateral or bilateral hearing loss of more than 15 dB Fletcher index was found in 13 of 51 (25.5%). Four of these 13 patients had a hearing loss of less than 20 dB in the worst ear. The remainder had a hearing loss of at least 30 dB in the worst ear. Five of the 13 patients had pure conductive hearing loss; in four of these five, a congenital origin was accepted. Two of the 13 had mixed hearing loss that was a residual symptom from previous otitis media; six had sensorineural hearing loss. A congenital cause was found in one of these six, based on the fact that she had been deaf and dumb since birth. In one other patient, noise-related deafness was likely (i.e., an acquired cause). In the other four cases in this group, the cause was unknown. The results of this study show that hearing loss is a characteristic associated with the Mayer-Rokitansky-Küster-Hauser syndrome.

Adult↗

Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation.

The aim of the present study was to investigate whether reducing the amount of luteinizing hormone (LH) in gonadotrophic preparations impairs follicular growth in in-vitro fertilization (IVF) cycles during suppression of endogenous LH levels. A selected group of 20 IVF patients was randomly divided into two groups. One group was treated with Org 31338 [follicle stimulating hormone (FSH)/LH 3:1], the other group with Metrodin (purified FSH), both during pituitary down-regulation with buserelin. A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrations of FSH, LH, oestradiol and progesterone were determined frequently and serial ultrasound examinations were performed. Multiple follicular growth with concomitant rise of oestradiol levels was observed in all cycles. The duration of the stimulation phase was shorter in the group treated with Org 31338 than in the group treated with Metrodin. The number of follicles and oocytes and the fertilization rate was larger and the mean embryo quality was higher in the Org 31338 group, but the differences did not reach statistical significance. No significant differences were found in hormonal values. In women with normal endocrine profiles, lowering of the LH activity in gonadotrophic preparations during gonadotrophin-releasing hormone agonist treatment results in adequate ovarian stimulation. However, a preparation with some LH needed a shorter stimulation than a purified FSH preparation. Whether the other beneficial effects of Org 31338 also occur in a larger population needs further investigation.

Adult↗

Mayer-Rokitansky-Küster-Hauser syndrome: distinction between two forms based on excretory urographic, sonographic, and laparoscopic findings.

OBJECTIVE: The purpose of this study was to discriminate typical (type A) from atypical (type B) Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (congenital absence of vagina and uterus) and determine their association with renal anomalies and ovarian disease. MATERIALS AND METHODS: The excretory urographic, sonographic, and laparoscopic findings in 91 patients with MRKH syndrome were compared retrospectively. Symmetric muscular buds and fallopian tubes were diagnostic of type A, and asymmetric muscular buds or abnormally developed fallopian tubes were diagnostic of type B. RESULTS: On the basis of laparoscopic findings, type A was diagnosed in 40 patients (44%) and type B was diagnosed in 51 patients (56%). Renal anomalies were found in 34 (37%) of the 91 patients, all of whom had type B syndrome. Renal agenesis and a pelvic kidney were the most common findings in the upper part of the urinary tract. Ovarian abnormalities were seen in 14 patients (15%), all of whom had type B syndrome. Sonography did not allow discrimination between types A and B in patients with normal kidneys (17/51 = 33%), but it provided important information in patients with associated cyclic abdominal pain, in cases of diagnostic dilemma, and in patients with associated renal anomalies. CONCLUSION: Discrimination between type A and type B of MRKH syndrome is important because associated renal and ovarian abnormalities occur only in type B. Laparoscopy is still needed to discriminate between these two forms. Sonography is useful for diagnosing cyclic abdominal pain and associated renal anomalies.

Abnormalities, Multiple↗

The unicornuate uterus: clinical implications.

The unicornuate uterus is associated with a poor reproductive outcome and many gynecological problems. We collected data from 45 women with a unicornuate uterus. We found a high abortion rate of 22% in the first trimester and 16% in the second trimester. Premature labor occurred in 18%. The prevalence of infertility and endometriosis in women with a unicornuate uterus was comparable to women without the anomaly.

Abortion, Spontaneous↗

Ultrasound diagnosis of interstitial pregnancy.

A case of interstitial pregnancy is reported. The diagnosis was made by ultrasound examination in an asymptomatic patient at risk for ectopic pregnancy following cornual anastomosis. Characteristic sonographic signs are discussed, with a review of the literature.

Adult↗

Spinal abnormalities and the atypical form of the Mayer-Rokitansky-Küster-Hauser syndrome.

In 96 patients with congenital absence of the uterus and upper vagina, the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, it proved possible to distinguish between the typical and the atypical form using laparoscopy. The typical form was characterized by symmetrical nonfunctioning muscular buds (the Müllerian duct remnants) and normal fallopian tubes, and the atypical form by aplasia of one or both buds, one bud smaller than the contralateral one, with or without dysplasia of one or both fallopian tubes. The atypical form was found in 52 patients (54.2%). Radiographs of the spine showed that congenital spinal abnormalities, especially the Klippel-Feil (KF) syndrome, were seen in 14 of the 52 patients with the atypical form only. Renal agenesis or ectopia together with the MRKH and KF syndromes, known as the MURCS association (MU: Müllerian duct aplasia; R: renal agenesis/ectopia; CS: cervical somite dysplasia), was diagnosed in 10/52 patients in the atypical group. From our results we conclude that additional cervical spine films in patients with the MRKH syndrome are indicated only in the atypical form the syndrome. In those cases where the MRKH syndrome is associated with the KF syndrome, the MURCS association should be considered.

Adolescent↗

On the origin and significance of serum CA-125 concentrations in 97 patients with endometriosis before, during, and after buserelin acetate, nafarelin, or danazol.

OBJECTIVE: To further elucidate the origin and significance of serum CA-125 in pelvic endometriosis. DESIGN: Retrospective. PATIENTS: Ninety-seven women with endometriosis who participated in two trials: (1) open-label study on buserelin acetate (n = 51) and (2) comparative, placebo-controlled study on nafarelin (n = 31) versus danazol (n = 15) (2:1 ratio). INTERVENTIONS: (1) Buserelin acetate 900 micrograms/d intranasally (IN); (2) nafarelin 400 micrograms/d IN versus danazol 400 mg/d orally during 6 months. MAIN OUTCOME MEASURE(S): Serum CA-125 and estradiol concentrations; severity of endometriosis-related symptoms; scores according to The American Fertility Society (AFS) classification for endometriosis and/or adhesions (before and on last day of therapy). RESULTS: Menstruation and adhesions appeared major factors influencing pretreatment serum CA-125 concentrations. Compared with nonmenstruating women without adhesions, both menses and adhesions induced a slight increase tending to significancy, whereas the elevating effect of adhesions and menses together was highly significant and more than expected. All three treatment regimens reduced CA-125 concentrations to the same extent; cessation of therapy was followed by restoration to pretreatment concentrations. Of the AFS scores for implants and/or adhesions, only pretreatment scores for adhesions correlated significantly with CA-125 concentrations. Severity scores for endometriosis-related complaints did not correlate. CONCLUSIONS: The findings indicate that adhesions play a major role in the presence of CA-125 in the systemic circulation and suggest that reductions of serum CA-125 concentrations during gonadotropin-releasing hormone agonist and danazol therapy are hormonally determined.

Antigens, Tumor-Associated, Carbohydrate↗