IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression

BACKGROUND: Down-regulation with GnRH agonist has been suggested to result in a profound suppression of LH bioactivity, reduced estradiol synthesis, and thus impaired IVF and pregnancy outcome. The aims of this study were: (i) to assess the usefulness of serum LH measurement on stimulation day 1 as a predictor of ovarian response, conception and pregnancy outcome in patients treated with long-term down-regulation with GnRH agonist and recombinant FSH, and (ii) to define the best threshold LH value, if any, to discriminate between women with different outcomes of IVF. METHODS: Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed. RESULTS: The range of LH concentrations on stimulation day 1 overlapped among non-conception cycles, conception cycles, ongoing pregnancies and early pregnancy losses. Receiver operating characteristic (ROC) analysis showed that serum LH concentrations on stimulation day 1 were unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.51; 95% CI: 0.49-0.54) or ongoing pregnancies versus early pregnancy loss groups (AUC(ROC) = 0.52; 95% CI: 0.47-0.57). Stratification for various low serum levels of LH did not reveal significant differences with respect to conception or pregnancy outcome among different LH levels on stimulation day 1. CONCLUSIONS: Serum LH concentration on stimulation day 1 cannot predict ovarian response, conception and pregnancy outcome in women receiving long-term down-regulation during assisted reproduction treatment.     

Effect of human hydrosalpinx fluid on the development of mouse embryos and role of the concentration of growth factors in culture medium with and without hydrosalpinx fluid.

The aim of this study was to investigate the effect of human hydrosalpinx fluid (HF) on the development and blastulation of mouse embryos and the role of the concentration of growth factors in culture medium with and without HF. In total, 2100 mouse embryos were cultured. Female mice were induced to superovulate and then mated with males. Two-cell-stage embryos were recovered from the oviduct and cultured in Ham's F-10 medium with bovine serum albumin and HF. Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) were analyzed by quantitative enzyme immunoassay. Mean blastulation index of 1.11, 0.97 and 0.98 was found at HF concentration of 5%, 20% and 30%, respectively (p = 0.8). The mean value of EGF in the control culture medium without HF was 11.2 pg/ml, which was statistically significantly different from that in culture medium containing HF (p < 0.001). The mean value of IGF-I in the control group without HF was 1.30 pg/ml and was not statistically significantly different from that in culture medium containing HF. Development of the two-cell-stage embryos was not affected at low (< 30%) HF concentrations. In conclusion, the present study demonstrates that even apparently normal blastulation is affected by any concentration of HF because of low embryonic EGF.     

Natural cycle IVF in unexplained, endometriosis-associated and tubal factor infertility.

BACKGROUND: To elucidate possible differences between unexplained and minimal peritoneal endometriosis-associated infertility, we studied their outcome in natural cycle IVF (NIVF). METHODS: A prospective cohort study was carried out on unexplained (33 couples), minimal peritoneal endometriosis-associated (30 couples) and tubal factor (24 couples) infertility in 223 NIVF cycles, using human chorionic gonadotrophin (HCG) for ovulation induction. RESULTS: During the first NIVF attempt, follicular and luteal phase oestradiol, FSH, LH and progesterone concentrations, as well as endometrial thickness and follicular diameter were similar among the three groups. Periovulatory follicular growth monitored from day of HCG administration to oocyte aspiration was significantly lowered in unexplained infertility compared with minimal endometriosis-associated and tubal factor infertility. The fertilization rate, clinical pregnancy rate per initiated cycle, per successful oocyte retrieval and per embryo transfer, in minimal endometriosis (80.0, 10.4, 16.0 and 23.5% respectively) were similar to that in tubal factor infertility patients (68.6, 5.8, 11.4 and 16.0%) but significantly higher (P < 0.05) than that of the unexplained infertility group (62.2, 2.6, 5.4 and 8.7%). CONCLUSIONS: The significant reduction in follicular periovulatory growth, fertilization and pregnancy rates in unexplained infertility compared with minimal peritoneal endometriosis patients may be explained by sub-optimal follicular development with possibly reduced oocyte quality, intrinsic embryo quality factors or by impaired implantation. From a clinical point of view, NIVF is less suited to unexplained infertility treatment, but might represent an interesting treatment option for minimal peritoneal endometriosis-associated infertility.     

Detecting depression after pregnancy: the validity of the K10 and K6 in Burkina Faso

OBJECTIVE: The K10 and K6 are short rating scales designed to detect individuals at risk for depressive disorder, with or without anxiety. Despite being widely used, they have not yet been validated for detecting postnatal depression. We describe the validity of these scales for the detection of postnatal depression in Burkina Faso. METHOD: The English language version of the K10 questionnaire was translated into West African French and local languages for use in Burkina Faso. Scores for 61 women were compared with the diagnostic interview made by a local psychiatrist within 3 days of administering the K10. RESULTS: Clinical assessment found that 27 (44%) women were probable cases of depression. Internal consistency of K10 and K6 scores, defined by Cronbach's alpha coefficient, was 0.87 and 0.78, respectively, indicating satisfactory reliability. The performance of the scores was not significantly different, with areas under the curve of 0.77 and 0.75 for the K10 and K6, respectively. To estimate prevalence of depression, we suggest cut-offs of > or =14 for the K10 and between > or =9 and > or =11 for the K6 for identifying women at high risk of depression. At > or =14, the K10 has 59% sensitivity, 91% specificity; at > or =10, the K6 has 59% sensitivity and 85% specificity. CONCLUSION: This study suggests that K10 and K6 are reasonably valid measures of depression among postpartum women in Burkina Faso and can be used as relatively cheap tools for estimating prevalence of postnatal depression in developing countries.     

Mortality after near-miss obstetric complications in Burkina Faso: medical, social and health-care factors

Objective

To investigate mortality in women in Burkina Faso in the 4 years following a life-threatening near-miss obstetric complication and to identify the medical, social and health-care-related causes of death.

Methods

In total, 1014 women were recruited after hospital discharge and followed for up to 4 years: 337 had near-miss complications and 677 had uncomplicated pregnancies. Significant differences in mortality between the groups were assessed using Fisher’s exact test. The medical causes of death were identified from medical records and verbal autopsy data; social and health-care-related factors associated with death were identified from interviews with the deceased women’s relatives.

Findings

In the 4 years, 15 (5.3%) women died in the near-miss group and 5 (0.9%) died after uncomplicated pregnancies (P < 0.001). More than half the deaths after a near miss, but none after an uncomplicated delivery, were pregnancy-related. Indirect factors contributed to many of these deaths, particularly human immunodeficiency virus infection. Relatives’ accounts suggested that the high cost and poor quality of health care, a lack of follow-up care and an unmet need for contraception contributed to the excess mortality in the near-miss group.

Conclusion

Women in Burkina Faso who initially survived a near-miss obstetric complication had an increased risk of all-cause and pregnancy-related death in the ensuing 4 years. The likelihood of survival over the longer term could be increased by offering a continuum of care that addresses the indirect and social causes of death and supplements the emergency intrapartum obstetric care provided by current safe motherhood programmes.     

The effect of metformin on ovarian stimulation and in vitro fertilization in insulin-resistant women with polycystic ovary syndrome: an open-label randomized cross-over trial.

Metformin effectively restores insulin sensitivity in insulin-resistant women with polycystic ovary syndrome (PCOS). We examined whether metformin, given prior to and during ovarian stimulation for in vitro fertilization (IVF), altered follicle stimulating hormone (FSH) requirement and increased the number of collected oocytes in these women. Seventeen insulin-resistant women with PCOS were recruited to our IVF unit to receive two consecutive cycles of ovarian stimulation with or without metformin co-treatment, the order of treatments being randomized using a table of random numbers. Metformin treatment (1500 mg/day) started 3 weeks before downregulation with buserelin acetate and was continued throughout ovarian stimulation with human recombinant FSH. Nine women completed both cycles, the results of eight women being excluded because of pregnancy after the first cycle (n = 4) or because the protocol of the study was not followed (n = 4). Mean total FSH dose was 2301 IU (range 1500-6563 IU) in metformin cycles and 2174 IU (range 1200-3900 IU) in parallel control cycles, while the mean number of collected oocytes was 8.6 (range 2-28) and 4.6 (range 1-16), respectively. Bayesian analysis showed probabilities of 0.05 that metformin reduces FSH requirement by at least 10%, and of 0.61 that at least 10% more oocytes are collected after metformin co-treatment. Co-administration of metformin is therefore likely to increase the number of oocytes collected after ovarian stimulation in insulin-resistant women with PCOS but is unlikely to reduce the requirement for FSH.     

A human tumor lung metastasis model in athymic nude rats

Experimental lung metastases regularly developed in athymic Han:rnu/rnu Rowett rats after i.v. injection of LOX human malignant melanoma cells. When 5 x 10(5) tumor cells were injected into 4-week-old rats, 89% of the animals died of lung tumors, with a mean survival time of 18 days. With 5- and 6-week-old rats, however, the fraction of animals that died decreased to 80 and 46%, with mean survival times of 35 and 38 days, respectively. The number of detectable lung colonies in each animal was about 35 in 5- and 6-week-old animals, compared to nearly 300 in 4-week-old rats. In the latter, a correlation was found between the number of tumor cells injected and the number of detectable lung colonies. The capacity of the LOX tumor to grow s.c. and to form experimental lung metastases was, by and large, similar in young nude rats and in nude mice, and no significant difference in morphology between the different tumors in the two species was seen. A high-resolution radiographic method was used to visualize lung colonies in the nude rats, and single tumors with diameters as small as 2-4 mm could be detected. By this method, for the first time, the effect of chemotherapy on a human tumor growing in a visceral organ of a rodent host could be followed by repeat X-ray examinations, mimicking a situation commonly faced in the clinic. This procedure may prove particularly useful for experimental chemotherapy studies, and may be extended to other human tumors that frequently metastasize to the lungs. Indications were obtained that some host-specific differences in tissue-preferenced growth might exist, a possibility that will be further explored.     

Effect of nickel chloride and cadmium acetate on the development of preimplantation mouse embryos in vitro

Preimplantation mouse embryos were used to investigate the toxic effect of nickel chloride and cadmium acetate on early embryo development in vitro.Embryos at the 2- and 4–8 cell stage were cultured in approximately 0.05 ml of mouse embryo culture medium (No. 16), overlaid with paraffin oil and incubated in a humidified atmosphere of 5% CO₂ in air for 48 h. NiCl₂ · 6H₂O was added to the culture medium at concentrations of 10–1000 μM, Cd(CH₃COO)₂ · 2H₂O at concentrations of 10–50 μM. Morphological criteria were used to check embryonic development.Ten micromolars of nickel chloride affected adversely the development of Day 2 embryos (2-cell stage), whereas 300 μM was needed to affect Day 3 embryos (8-cell stage). Toxic effect of cadmium acetate on Day 2 embryos was observed at a concentration of 10 μM.     

Intracytoplasmic sperm injection (ICSI) in unexplained and stage I endometriosis-associated infertility after fertilization failure with in vitro fertilization (IVF)

Purpose: To investigate possible differences between unexplained and stage I endometriosis-associated infertility in ICSI cycles conducted after low fertilization (<20%) in preceding IVF cycles with normal semen parameters. Methods: Retrospective cohort study consisting of patients with unexplained (n=48) and stage I endometriosis-associated infertility (n=43) with a minimum of one IVF cycle with <20% fertilized oocytes and normal semen quality, treated with ICSI from January 1997 to January 2006. Age matched male factor infertility patients (n=91) were used as controls. Results: Diploid fertilization rate was significantly lower in the stage I endometriosis-associated infertility group compared to the unexplained infertility group. Score of the transferred embryos, implantation rate, pregnancy rate and outcome were similar in the two groups. Conclusions: ICSI appears to be an efficient treatment option after fertilization failure with IVF in unexplained and stage I endometriosis-associated infertility.     

Follicle-stimulating hormone receptor gene mutations are not evident in Greek women with premature ovarian failure and poor responders

BACKGROUND/AIMS: This clinical and molecular study aimed to investigate the presence of follicle-stimulating hormone (FSH) receptor gene mutations in women with premature ovarian failure (POF) and poor responders to in vitro fertilization treatment. METHODS: DNA was extracted from blood samples for subsequent polymerase chain reaction (PCR). PCR was followed by restriction fragment length polymorphism and direct sequencing. RESULTS: No inactivating mutations reported so far were identified in exons 6, 7, and 10 in women with POF and poor responders. CONCLUSION: FSH receptor gene mutations are not frequent in Greek patients with POF as is the case in the rest of the world except for cases with ovarian dysgenesis in Finland.