Willem Ombelet

Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation.

There is now some evidence that i) the availability of plasma tryptophan, the precursor of serotonin, is significantly lower in pregnant women at the end of term and the first few days after delivery than in nonpregnant women; and ii) both pregnancy and the early puerperium are accompanied by activation of the inflammatory response system. The aims of the present study were to examine the effects of pregnancy and delivery on plasma kynurenine, a major tryptophan catabolite synthesized after induction of indoleamine-2, 3 dioxygenase (IDO) by pro-inflammatory cytokines. We measured plasma kynurenine and tryptophan and immune markers, such as serum interleukin-6 (IL-6), IL-8 and the leukemia inhibitory factor-receptor (LIF-R) in healthy, nonpregnant and pregnant women at the end of term and one and three days after delivery. Plasma kynurenine was significantly lower in pregnant women at the end of term than in nonpregnant women, findings which may be attributed to lower plasma tryptophan at the end of term. The kynurenine/tryptophan (K/T) quotient was significantly higher in the pregnant women at the end of term and in the early puerperium than in nonpregnant women. In the early puerperium there was a significant increase in plasma kynurenine and the K/T quotient. The increases in plasma kynurenine and the K/T quotient were significantly more pronounced in women whose anxiety and depression scores significantly increased in the puerperium. The changes from the end of term to the early puerperium in plasma kynurenine and the K/T quotient were significantly related to those in the immune markers. It is concluded that 1) lower plasma kynurenine at the end of term is the consequence of lower plasma tryptophan; 2) the increased K/T quotient at the end of term and in the early puerperium indicates inflammation-induced degradation of tryptophan along the kynurenine pathway; and 3) that depressive and anxiety symptoms in the early puerperium are (causally) related to an increased catabolism of tryptophan into kynurenine, a phenomenon which probably results from immune activation.

Immune activation in the early puerperium is related to postpartum anxiety and depressive symptoms

The pathophysiology of the postpartum blues, common transient mood disorders in the first week postpartum, has remained elusive. Recently, however, it has been shown that depression and anxiety disorders are accompanied by activation of the inflammatory response system (IRS). This study was developed to determine whether the postnatal blues is associated with IRS activation. Serum concentrations of interleukin-6 (IL-6), IL-6 receptor (IL-6R), gp130 (the IL-6 signaling protein), IL-1R antagonist (IL-1RA) and leukemia inhibitory factor receptor (LIFR) were assayed in 22 nonpregnant women and in 91 pregnant women before delivery and 1 and 3 days after delivery. On each occasion the parturient women completed the State version of the Spielberger State-Trait-Anxiety-Inventory (STAI) and the Zung Depression Rating Scale (ZDS). Serum IL-6, IL-1RA and LIFR were significantly higher in pregnant women at the end of term than in nonpregnant women.

Semen quality and intrauterine insemination

There is good evidence in literature that intrauterine insemination (IUI) is the best first line treatment and most cost-effective procedure for moderate male factor subfertility. It seems very difficult to identify individual semen parameters predicting the likelihood of pregnancy after IUI. This can be explained by a lack of standardization of semen analysis, but many other methodological variables may also influence IUI success rates such as the patient selection, type of ovarian stimulation and number of inseminations per cycle. A review of the literature confirmed that sperm morphology using strict criteria and the inseminating motile sperm count (IMC) after sperm preparation are the two most important sperm parameters to assess the real impact of semen quality on IUI outcome. A universal threshold level above which IUI can be performed with acceptable pregnancy rates has not been determined yet, although IUI success seems to be impaired with <5% normal spermatozoa and an IMC of <1 x 10(6). Until now, no method of sperm preparation has been shown to be superior with regard to pregnancy rate after IUI. Whether supplementation of culture media with substances such as antioxidants and platelet activating factor may improve the results remains the subject of further research.

The inflammatory response following delivery is amplified in women who previously suffered from major depression, suggesting that major depression is accompanied by a sensitization of the inflammatory response system

BACKGROUND There is now evidence that some patients with major depression show an activation of the inflammatory response system (IRS). This study was carried out to examine whether major depression may induce sensitization with increased IRS responses to the stress of child birth. METHODS Serum concentrations of interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R), sgp130 (the IL-6 signal transducing protein) and the sIL-1R antagonist (sIL-1RA) were determined in 16 and 50 women with and without a lifetime history of major depression, respectively. Blood was collected 3-6 days before delivery and 1 and 3 days after delivery. On each occasion the women completed the Zung Depression Rating Scale (ZDS). RESULTS Serum IL-6, sIL-6R, sIL-1RA were significantly higher 1 and 3 days after delivery than before. Women who had suffered from a lifetime history of major depression had greater increases in serum IL-6 and sIL-1RA in the early puerperium than women without a lifetime history. Women who had suffered from a lifetime history of major depression had significantly higher IL-6, and sIL-1RA concentrations 1 and 3 days after delivery than women with a negative life-time history. CONCLUSIONS The responses of IL-6 and sIL-1RA following delivery are amplified in women who previously suffered from major depression. The results suggest that major depression is accompanied by a sensitization of the IRS.

Affordable IVF for developing countries

Worldwide, more than 80 million couples suffer from infertility; the majority are residents of developing countries. Residents of developing countries encounter a lack of facilities at all levels of health care, but especially infertility diagnosis and treatment. Infertility defined as a disease has a much stronger negative consequence in developing countries compared with Western societies. Social isolation, economic deprivation and violence are commonly observed. Tubal infertility due to sexually transmitted diseases, unsafe abortion and post-partum pelvic infections are the main causes of infertility in developing countries. Very often those conditions are only treatable by assisted reproductive technologies. Although preventative measures are undoubtedly the most cost-effective approach, not offering assisted reproduction is not an alternative. This study proposes a specially designed infertility care programme leading to cost-effective simplified assisted reproduction as a valid treatment protocol in developing countries when prevention or alternative methods have failed. Special attention should be given to avoid adverse outcomes such as ovarian hyperstimulation and multiple embryo pregnancy.

A prospective study to evaluate the anatomic and functional outcome of a transobturator mesh kit (prolift anterior) for symptomatic cystocele repair.

The objective of this study was to estimate the anatomical and functional outcome of Prolift Anterior C. All patients presenting with symptomatic stage II or greater anterior vaginal wall prolapse were considered to enter this prospective observational study. Patient characteristics and surgical parameters were prospectively documented. Anatomical outcome, as measured by the Pelvic Organ Prolapse Quantification (POP-Q) score, and functional outcome, as assessed by the Kings College Health Questionnaire, was considered primary outcome measures. Complications constituted the secondary outcome measures. Fifty-one patients met the inclusion criteria, and 48 underwent a transobturator anterior vaginal wall mesh. Objective cure was realized in 46 out of 48 (95.8%) patients. Postoperatively, 5 out of 48 (10.4%) patients developed an erosion which required surgical intervention in 2 (4.3%) patients. Subjective cure was achieved in 40 out of 42 (95.2%) patients. Urgency symptoms persisted in 3 out of 21 (14%). De novo urgency and frequency developed in only 1 patient. De novo stress incontinence developed in 4 out of 30 (13%). In 9 out of 29 (31%) of sexually active patients, dyspareunia due to the prolapse was present before surgery and disappeared in all; 3 out of 20 (15%) reported de novo dyspareunia. In conclusion, we state that transobturator anterior vaginal wall mesh kits provide a surgical tool with an acceptable but real morbidity to treat anterior vaginal wall prolapse with a favorable objective and subjective outcome.

Pregnancy after ICSI with ejaculated immotile spermatozoa from a patient with immotile cilia syndrome: a case report and review of the literature

This study presents a case of intracytoplasmic sperm injection (ICSI) with ejaculated immotile spermatozoa from a patient with immotile cilia syndrome. Semen analysis of the patient suffering from immotile cilia syndrome revealed an extreme oligoasthenoteratozoospermia (OAT: count <1.4 x 10(6)/ml, 0% motility and 3% normal morphology). Electron microscopy of sperm flagella showed the absence of inner and outer dynein arms. During the ICSI cycle, the hypo-osmotic swelling test (HOS) was used for the identification of viable spermatozoa in the pool of immotile spermatozoa for ICSI. A normal fertilization rate was found in eight out of the 12 oocytes. A first fresh double embryo transfer resulted in a late miscarriage at 21 weeks. A second healthy singleton pregnancy occurred after transfer of two frozen-thawed embryos from the same ICSI procedure. Although only one successful ICSI case of the immotile cilia syndrome combined with HOS is described here, HOS might be a simple but valuable tool to obtain normal fertilization and pregnancy for patients suffering from immotile spermatozoa.

Semen quality and prediction of IUI success in male subfertility: a systematic review

Many variables may influence success rates after intrauterine insemination (IUI), including sperm quality in the native and washed semen sample. A literature search was performed to investigate the threshold levels of sperm parameters above which IUI pregnancy outcome is significantly improved and/or the cut-off values reaching substantial discriminative performance in an IUI programme. A search of MEDLINE, EMBASE and Cochrane Library revealed a total of 983 papers. Only 55 studies (5.6%) fulfilled the inclusion criteria and these papers were analysed. Sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value ⩾5% normal morphology; (iii) total motile sperm count in the native sperm sample: cut-off value of 5-10 million; and (iv) total motility in the native sperm sample: threshold value of 30%. The results indicate a lack of prospective studies, a lack of standardization in semen testing methodology and a huge heterogeneity of patient groups and IUI treatment strategies. More prospective cohort trials and prospective randomized trials investigating the predictive value of semen parameters on IUI outcome are urgently needed. It is generally believed that intrauterine insemination (IUI) with homologous semen should be a first-choice treatment to more invasive and expensive techniques of assisted reproduction in cases of cervical, unexplained and moderate male factor subfertility. The rationale for the use of artificial insemination is to increase gamete density at the site of fertilization. Scientific validation of this strategy is difficult because literature is rather confusing and inconclusive. Many variables may influence success rates after IUI treatment procedures. It seems logical that sperm quality has to be one of the main determinants to predict IUI success. Clinical practice would benefit from the establishment of threshold levels for sperm parameters above which IUI pregnancy outcome is significantly improved and below which a successful outcome is unlikely. We performed a literature search to investigate if such threshold levels are known. Most striking were the lack of standardization in semen-testing methodology and the huge heterogeneity of patient groups and IUI treatment strategies. The four sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value >4% normal morphology; (iii) total motile sperm count in native sperm sample: cut-off value of 5-10 million; and (iv) total motility in native sperm sample: threshold value of 30%. This review identified an urgent need for more and better prospective cohort trials investigating the predictive value of semen parameters on IUI pregnancy rate.

Obstetric and perinatal outcome of 1655 ICSI and 3974 IVF singleton and 1102 ICSI and 2901 IVF twin births: a comparative analysis

A total of 3974 IVF and 1655 ICSI singleton births and 2901 IVF and 1102 ICSI twin births were evaluated. Pregnancies after both fresh and frozen transfers were included. IVF and ICSI singleton pregnancies were very similar for most obstetric and perinatal variables. The only significant difference was a higher risk for prematurity (< 37 weeks of amenorrhoea) in IVF pregnancies compared with ICSI pregnancies (12.4 versus 9.2%, OR = 1.39, 95% CI = 1.15-1.70). For twin pregnancies, differences were not statistically different except for a higher incidence of stillbirths in the ICSI group (2.08 versus 1.03%, OR = 2.04, 95% CI = 1.14-3.64). Intrauterine growth retardation with or without pregnancy-induced hypertension was observed more often in the ICSI group. Regression analysis of the data with correction for parity and female age showed similar results for twins. For singletons, this analysis showed similar results with the exception of low birth weight babies (< 2500 g), which were also observed more often in IVF pregnancies (9.6 versus 7.9%, OR = 0.79, CI = 0.65-0.98, P = 0.03). This large case-comparative retrospective analysis showed that the obstetric outcome and perinatal health of IVF and ICSI pregnancies is comparable.

The influence of anaesthetic techniques and type of delivery on peripartum serum interleukin-6 concentrations

Background: Interleukin‐6 is a pleiotropic cytokine with a wide range of physiological activities. It plays an important role in the immuno‐neuro‐humoral axis during stress and surgery.