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Introduction: Weight loss amongst women with polycystic ovary syndrome (PCOS) is crucial to reduce the risk of endocrine, reproductive and metabolic complications including hirsutism, menstrual disturbances and cardiovascular disease.... more
Introduction: Weight loss amongst women with polycystic ovary syndrome (PCOS) is crucial to reduce the risk of endocrine, reproductive and metabolic complications including hirsutism, menstrual disturbances and cardiovascular disease. With approximately 50% of women with PCOS being overweight or obese, effective dietary management of weight in PCOS is essential. However, there is inconsistent evidence as to whether specifically modified diets (e.g. reduced carbohydrate diets) are more effective at achieving weight loss amongst women with PCOS than are conventional healthy hypocaloric diets. Material and Methods: A systematic review and meta-analysis of randomized controlled trials that had compared weight and BMI between women with PCOS who had undergone either a specifically modified diet or a conventional healthy hypocaloric diet were performed. Six electronic databases were searched, a manual search of the reference lists of the included studies was carried out and authors were contacted for additional information. Nine studies with a total of 395 participants (all with a body mass index [BMI] ≥30) were included in the meta-analysis. The effect size used was the mean difference in post-intervention weight and BMI between participants who had undergone a specifically modified diet and participants who had undergone a conventional healthy hypocaloric diet. Results: There were no differences between groups in post-intervention weight (mean difference 1.26, 95% confidence interval (CI) -0.92 to 3.43, p = .26; heterogeneity I2 = 50%, p = .04) or BMI (mean difference 0.15, 95% CI -0.93 to 1.23, p = 0.79; heterogeneity I2 = 44%, p = 0.10). Subgroup analyses according to the presence of a dietary run-in period (a period at the start of the study during which all participants are placed on an identical diet in order to equalize them on variables influenced by diet), intervention duration and type of diet and a sensitivity analysis according to study quality were not significant. Conclusions: Whilst the results should be interpreted in light of the moderate heterogeneity observed, they suggest that specifically modified diets offer no added benefit for weight loss in women with PCOS over conventional healthy hypocaloric diets. The findings of this meta-analysis may promote the unification of guidelines for the dietary management of PCOS and allow clinicians to be confident in prescribing conventional healthy hypocaloric diets for weight loss amongst their PCOS patients.
Equatorial compression of the fetal head is known to occur during labor; its effect on trancutaneous scalp PO2 (PtCO2) was investigated in acute experiments in four fetal lambs. Fetal PtCO2, and oxygen tension (PaO2) and flow in a carotid... more
Equatorial compression of the fetal head is known to occur during labor; its effect on trancutaneous scalp PO2 (PtCO2) was investigated in acute experiments in four fetal lambs. Fetal PtCO2, and oxygen tension (PaO2) and flow in a carotid artery were continuously measured. Equatorial head compression was obtained by inflating a cuff around the fetal head. A strong relationship was shown to exist between PtCO2 and PaO2 values in the normoxemic and hypoxemic fetus. Stepwise compression of the fetal head resulted in a PtCO2 of zero at cuff pressures of 40 to 50 mmHg. Laborlike fetal head compression with an intensity of 50 to 70 mmHg and a duration of one minute resulted in a 30 to 60% fall in PtCO2. Fetal PaO2 remained stable in all experiments. The present findings indicate that values of PtCO2 during fetal head compression do not reflect fetal arterial oxygen tension. This questions the reliability of transcutaneous PO2 monitoring as a method of intrapartum surveillance.
Ovarian cysts from 27 selected patients were examined cytologically as well as histologically. The aspirates were obtained by means of ultrasound or laparoscopy. Cytological examination in 17 of the cases did not show malignancy, but... more
Ovarian cysts from 27 selected patients were examined cytologically as well as histologically. The aspirates were obtained by means of ultrasound or laparoscopy. Cytological examination in 17 of the cases did not show malignancy, but histological examination demonstrated malignancy in 5 of these patients. The fluid of the other 10 cysts indicated malignancy, which was confirmed histologically in only 4 cases. From this study we conclude that cytological examination has little to offer in diagnosing the true nature of ovarian cysts.
There is good evidence that transcutaneously measured oxygen tension (P tc O 2 ) in newborns and adults closely reflects central arterial oxygenation. However, doubts have been expressed with regard to the agreement between fetal scalp P... more
There is good evidence that transcutaneously measured oxygen tension (P tc O 2 ) in newborns and adults closely reflects central arterial oxygenation. However, doubts have been expressed with regard to the agreement between fetal scalp P tc O 2 and systemic fetal oxygenation during labor. The values of fetal scalp P tc O 2 could be altered independently of fetal arterial PO 2 (PaO 2 ) due to compression of the fetal scalp capillary circulation by the pressure circle that develops between the fetal presenting part and the birth canal during uterine contractions. This chapter provides the findings of a study involving experimental head compression and transcutaneous oxygen tension in the fetal lamb. The comparison of values was obtained by continuous transcutaneous measurement of fetal scalp PO 2 and by continuous monitoring of fetal arterial oxygen tension shows good agreement during normoxemia and hypoxemia in the absence of fetal head compression. This confirms the previous reported accuracy of the transcutaneous and intravascular PO 2 transducers used in this study. On the basis of these experiments, the possibility cannot be excluded that a decreased intracranial oxygen delivery because of the fall in carotid artery flow that occurs during fetal head compression may in part be responsible for the fall in P tc O 2 .
Propagation of electrical (EMG) activity in the myometrium may be facilitated by the presence of gap junctions (GJ), leading to improved synchronization of contractility. EMG and mechanical (IUP) activity in relation to GJ area were... more
Propagation of electrical (EMG) activity in the myometrium may be facilitated by the presence of gap junctions (GJ), leading to improved synchronization of contractility. EMG and mechanical (IUP) activity in relation to GJ area were studied in 9 periparturient and in 2 ovariectomized (OVX) oestradiol-17 beta (E2) treated ewes, chronically instrumented with bipolar electrodes and intrauterine sponge-tip catheters. Myometrial biopsies were taken under epidural anaesthesia at various time intervals around delivery and after intra-arterial administration of 0.1 mg of E2. In pregnant ewes we found a significant increase in the rate of rise and area of IUP cycles during labour. Both were closely related to a significant increase in GJ area. In E2 treated OVX sheep we found a significant increase in GJ area, with a maximum at 24 hours after injection. The increase in GJ area was associated with a significant increase in the rate of rise of IUP cycles. The results of our study support the h...
The objective was to elucidate the functional relationship between estradiol-induced changes in myometrial activity, uterine prostanoid synthesis, and gap junction formation in vivo. The study design was as follows. The effects of... more
The objective was to elucidate the functional relationship between estradiol-induced changes in myometrial activity, uterine prostanoid synthesis, and gap junction formation in vivo. The study design was as follows. The effects of inhibition of prostanoid synthesis with naproxen on formation of gap junctions and coordination of electrical and mechanical myometrial activity induced by estradiol-17 beta were investigated in 6 chronically instrumented oophorectomized ewes. Prostanoid metabolites were measured in arterial and uterine venous plasma. Myometrial biopsies were obtained to determine gap junction area. The results were that intraarterial administration of 0.1 mg of estradiol-17 beta was followed by a significant increase in maximum rate of rise of the intrauterine pressure cycles and a significant decrease in conduction time of bursts of electrical activity; this response was not altered by pharmacologic inhibition of uterine prostanoid synthesis using naproxen. Estradiol administration during continuous naproxen infusion increased gap junction area. The conclusion is that improved coordination of myometrial activity and formation of myometrial gap junctions induced by estradiol is not mediated by prostaglandins.
In 10 chronically instrumented pregnant ewes myometrial electrical activity and intrauterine pressure were measured and plasma levels of 17 beta-estradiol and progesterone were determined in late pregnancy and during and after labor.... more
In 10 chronically instrumented pregnant ewes myometrial electrical activity and intrauterine pressure were measured and plasma levels of 17 beta-estradiol and progesterone were determined in late pregnancy and during and after labor. Myometrial biopsies were obtained to determine gap junction area. Plasma progesterone levels fell 4 days before delivery, and 17 beta-estradiol levels rose sharply 12 hours before delivery. Toward delivery the myometrial electrical pattern changed from infrequent bursts of long duration to frequent bursts of short duration, and the active pressure area of the intrauterine pressure cycles, the apparent conduction velocity, and the rate of rise of intrauterine pressure cycles increased associated with the changes in hormone levels. These changes were related to an increase in gap junction area. It is concluded that these results support the hypothesis that changes in concentrations of steroid hormones lead to an increase in myometrial gap junction area, which improves the coordination of contractile activity of the uterus during labor.
Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation
Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation
Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation
The results of in-vitro fertilization (IVF) treatments carried out in a university IVF centre are compared with those obtained following 15-40 min transportation of oocytes from a transport IVF clinic to the central IVF laboratory of the... more
The results of in-vitro fertilization (IVF) treatments carried out in a university IVF centre are compared with those obtained following 15-40 min transportation of oocytes from a transport IVF clinic to the central IVF laboratory of the university centre. Moreover, treatment results following monitoring of ovarian stimulation in satellite clinics, combined with ovum retrieval at the transport clinic and transport of oocytes to the central IVF laboratory, are described. In a total of 5540 IVF treatment cycles, 24-26% of viable pregnancies per embryo transfer were found in the three groups. Comparison of results, obtained with the three different treatment modalities, showed no negative influences of transporting oocytes from transport clinic to IVF laboratory and of monitoring ovarian stimulation in satellite clinics. It is concluded that decentralization of the clinical phase of IVF treatment is possible. This leads to a more optimal use of existing laboratory facilities in large urban areas. It is stressed that good communication between satellite clinic, transport clinic and IVF laboratory is necessary for a decentralized IVF programme. To obtain good quality assurance, both the satellite clinic and the transport clinic must adhere to the same protocol.
Research Interests:
To compare efficacy, safety and patient preference of a single oral dose of 150 mg fluconazole with a single intravaginal dose of 1200 mg miconazole in vaginal candidosis. To investigate the effect of treatment on Candida colonization of... more
To compare efficacy, safety and patient preference of a single oral dose of 150 mg fluconazole with a single intravaginal dose of 1200 mg miconazole in vaginal candidosis. To investigate the effect of treatment on Candida colonization of throat and rectum. Double-blind, double-dummy, parallel, randomized trial. Ninety-nine patients with symptomatic and mycologically verified candidosis were given 150 mg fluconazole with an intravaginal dummy, or 1200 mg miconazole with an oral dummy. Patients with an inadequate short-term response were given a second dose. At each visit a patient self assessment and an investigators' global assessment were recorded, and cultures were set up. Adverse events were recorded and laboratory tests were performed. Clinical cure or improvement (investigators' assessment) was obtained in 100% (short-term) and 95% (long term) of the fluconazole group and in 94% and 90%, respectively, of the miconazole group. Patients considered the treatment excellent or good in 81% (short-term) and 88% (long-term) in the fluconazole group and in 84% and 76%, respectively, of the miconazole group. Mycological cure was achieved in 98% (short-term) and 73% (long-term) of the fluconazole group and in 96% and 82% respectively in the miconazole group. The differences in results were not significant. Both treatments significantly reduced the number of positive rectal cultures: neither treatment had a significant effect on throat cultures. Four percent of the patients preferred intravaginal therapy. A single dose fluconazole is as safe and effective as a single dose of miconazole.
retrieval for in-vitro fertilization and embryo transfer
Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian... more
Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian response (AFC < 11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC < 11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to ...
A case of appendicitis following transvaginal oocyte retrieval is presented. The time sequence and the finding of puncture holes in the appendix indicate a causal relationship between the two events. Although minor infectious... more
A case of appendicitis following transvaginal oocyte retrieval is presented. The time sequence and the finding of puncture holes in the appendix indicate a causal relationship between the two events. Although minor infectious complications have been reported previously, this is the first report of appendicitis caused by transvaginal oocyte retrieval.
Four different major clinical complications were identified in a retrospective analysis of 2495 in-vitro fertilization (IVF) cycles resulting in oocyte retrieval. The severe form of ovarian hyperstimulation syndrome (OHSS) occurred in 18... more
Four different major clinical complications were identified in a retrospective analysis of 2495 in-vitro fertilization (IVF) cycles resulting in oocyte retrieval. The severe form of ovarian hyperstimulation syndrome (OHSS) occurred in 18 patients, giving a prevalence for this complication of 0.7%. Seven (39%) of these 18 patients had previously been diagnosed as having polycystic ovaries. Eleven patients were admitted with moderate OHSS. Adnexal torsion was diagnosed in two patients. Ovariectomy was considered necessary in both cases. Complications of the transvaginal procedure occurred in seven cases (0.3%): one patient had an acute appendicitis with puncture holes in the appendix, six patients were admitted shortly after oocyte retrieval with a pelvic inflammatory disease. Of the 624 pregnancies obtained, 13 were ectopic, giving an ectopic pregnancy rate of 2.1%. It is concluded that serious clinical complications of IVF treatment are rare. However, patients should be counselled for the occurrence of serious procedure-related complications before entering an IVF programme.
Controlled ovarian hyperstimulation could lead to opposing effects on thyroid function. Therefore, in a prospective study of 65 women under- going controlled ovarian hyperstimulation, thyroid hormones, T4-bind- ing globulin, TPO... more
Controlled ovarian hyperstimulation could lead to opposing effects on thyroid function. Therefore, in a prospective study of 65 women under- going controlled ovarian hyperstimulation, thyroid hormones, T4-bind- ing globulin, TPO antibodies, gonadotropins, estradiol, and PRL were measured before and after controlled ovarian hyperstimulation. After ovarian stimulation (mean 6 SE of mean): free T4 de- creased, 14.4 6 0.2 vs. 12.9
The chance of recurrence of poor fertilization in a second in vitro fertilization (IVF) cycle was assessed. Total fertilization failure was defined, and the relationship between the fertilization rate and the number of motile sperm cells... more
The chance of recurrence of poor fertilization in a second in vitro fertilization (IVF) cycle was assessed. Total fertilization failure was defined, and the relationship between the fertilization rate and the number of motile sperm cells per milliliter of semen was assessed. Patients with a total fertilization failure or poor fertilization (20% or less of the oocytes fertilized) were divided into three subgroups with different chances of fertilization and were followed in a subsequent IVF cycle. The recurrence rate of total fertilization failure was high in all three groups (45-70%), and poor fertilization frequently occurred in the second cycle (50-75%). Poor fertilization frequently recurs in the second IVF cycle. The use of intracytoplasmic sperm injection could be considered after fertilization of 20% or less of oocytes in the first cycle, irrespective of the number of motile sperm cells per milliliter of semen.
To determine whether age or response to controlled ovarian hyperstimulation (COH) is a better predictor of IVF outcome in women > or = 40 years. Retrospective analysis. A transport IVF program. For patients undergoing IVF treatment the... more
To determine whether age or response to controlled ovarian hyperstimulation (COH) is a better predictor of IVF outcome in women > or = 40 years. Retrospective analysis. A transport IVF program. For patients undergoing IVF treatment the correlation between treatment outcome and age and response to COH was analyzed using the data of 2,588 consecutive cycles. None. Pregnancy. The incidence of poor ovarian response rises significantly with increasing age. Analysis of all cycles showed a significant decrease in clinical and ongoing pregnancy rate for women > or = 40 years. Analysis of cycles with a good ovarian response showed no statistically significant differences for these parameters between women > or = 40 years and those younger. A logistic regression analysis on pregnancy showed that ovarian response contributes more to the prediction of pregnancy than age. Patients aged > or = 40 years with a good response to COH have a good prognosis for IVF treatment. The age limit ...
Embryo transfer results after a 2 to 4 day period of embryo culture were compared. Two thousand two hundred ninety-seven ETs, performed in 1991 and 1992, were analyzed. Ongoing pregnancy rates after 2, 3, or 4 days of embryo culture were... more
Embryo transfer results after a 2 to 4 day period of embryo culture were compared. Two thousand two hundred ninety-seven ETs, performed in 1991 and 1992, were analyzed. Ongoing pregnancy rates after 2, 3, or 4 days of embryo culture were 23.3%, 21.9%, and 26.4%, respectively. Multiple pregnancy rates were 36.2%, 38.8%, and 32.6% per ongoing pregnancy for the three groups, respectively. The implantation rate of 73 cavitating morulae on day 4 was surprisingly high (41%) compared with that of other developmental stages. Transfer after 4 days of culture gives the ability to recognize embryos with a very high implantation potential.
To investigate the feasibility of IVF treatment with minimal monitoring during ovarian hyperstimulation. Retrospective analysis and prospective study with real-time control group. Transport IVF program with transport clinic and satellite... more
To investigate the feasibility of IVF treatment with minimal monitoring during ovarian hyperstimulation. Retrospective analysis and prospective study with real-time control group. Transport IVF program with transport clinic and satellite clinics. One hundred consecutive IVF cycles monitored at a transport clinic and 100 concurrent consecutive cycles monitored at satellite clinics, using the same stimulation-monitoring protocol and resulting in oocyte aspiration, are compared retrospectively for the number of ultrasound (US) measurements carried out during monitoring and for results of IVF treatment. No patient selection took place. After introduction of a minimal monitoring protocol at a transport clinic, a prospective study was started comparing 100 minimal monitoring cycles at a transport clinic with 100 concurrent conventional monitoring cycles at satellite clinics, all resulting in oocyte aspiration. Patients entered the retrospective or prospective study only once. In all cases...
A prospective controlled study was performed to compare the PRs obtained after use of a uniform IVF culture medium containing a pasteurized serum protein solution or patient serum. The ongoing PRs per ET in the serum and the protein... more
A prospective controlled study was performed to compare the PRs obtained after use of a uniform IVF culture medium containing a pasteurized serum protein solution or patient serum. The ongoing PRs per ET in the serum and the protein solution group were 32% and 28%, respectively (not significant). Culture of supernumerary embryos showed blastocyst formation and even hatching with both supplements. The PR will not drop when this protein solution is used as a protein supplement in IVF culture medium instead of patient serum.

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