Chronic liver disease and liver transplantation (LT) can delay both timing and ability of women to conceive. With increased awareness and availability of in vitro fertilisation (IVF), the need for ...accurate counselling is paramount. To date, minimal data exist on outcomes of IVF in patients with chronic liver disease, cirrhosis, or post-LT. We report the largest experience of IVF in women with liver-related subfertility (LRSF).
A retrospective analysis was performed on 42 women with LRSF who had undergone 57 IVF cycles between 1990 and 2019.
Forty-two women with LRSF received IVF; 9 cycles in 6 women with cirrhosis, 14 cycles in 11 women post-LT, and 34 cycles in 25 women without cirrhosis. The main aetiologies of liver disease included HBV, HCV, and autoimmune hepatitis (AIH). Of 57 IVF cycles evaluated, 43 (75%) resulted in successful implantation. Eight (2 post-LT, 3 with cirrhosis, 4 without cirrhosis) resulted in miscarriage. The live birth rate (LBR) was 74% (32/43). Two of 9 (22%) patients with cirrhosis, 4/14 (29%) patients who were post-LT, and 6/34 (18%) patients without cirrhosis had unsuccessful IVF attempts. Nine of 57 (16%) IVF cycles resulted in new liver enzyme derangement during therapy, which improved after treatment completion. Six pregnancies (2 in patients who were post-LT, 4 without cirrhosis) were complicated by obstetric cholestasis (OC). Ovarian hyperstimulation syndrome (OHSS) was rare (n = 3, 7%). One patient with AIH-related cirrhosis decompensated after initiating IVF, warranting discontinuation of therapy. There were no maternal deaths. Three women developed a hypertensive disorder of pregnancy. Half the pregnancies resulted in premature deliveries (range 27–36 weeks).
In selected cases, IVF in women with LRSF can be successful. However, patients should be counselled on the potential increased risks of OHSS, OC, and prematurity.
Women with liver disease or those who have had a liver transplant can experience difficulties getting pregnant. In this study, we look at whether alternative approaches to achieve pregnancy are harmful in these women. Overall, there were no significant issues with the use of in vitro fertilisation in women with liver disease, but they need to be aware of potential risks, such as early delivery of the baby.
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•Subfertility is common in women with liver disease and can persist post-LT.•Although the complications of IVF are well described in the general population, its effects on women with liver disease are unknown.•Women with LRSF can undergo successful pregnancies with IVF therapy.•Complications are potentially greater in women with liver disease, so pre-conception counselling is important.
In order to maximize In vitro fertilization (IVF) success rates in advanced- age patients, it has been suggested to favor the use of intracytoplasmic sperm injection (ICSI) over conventional ...insemination (CI), with the notion that ICSI would serve as a tool to overcome interference in sperm oocyte interaction and sperm oocyte penetration issues that can be related to maternal age and are not due to sperm abnormalities. We therefore aim to evaluate the role of ICSI in the treatment of non-male factor infertile patients aged ≥35 in terms of fertilization and top-quality embryo rates.
In this retrospective cohort study, data were collected and analyzed for all patients with non-male factor infertility, aged ≥35 treated, undergoing their first IVF cycle attempt with 6 or more oocytes yield, in whom a 50% ICSI-CI division was performed.
Five hundreds and four oocytes were collected from 52 eligible patients. Overall, 245 oocytes underwent ICSI and 259 oocytes underwent CI. The fertilization rate was 71.0% following ICSI, compared to 50.1% in the CI treated oocytes (P < 0.001). The top quality embryo rate was 62.8% following ICSI compared to 45.5% following CI (P < 0.001). Subdividing the study population to two age groups revealed that the above differences remained significant in patients aged 35-39 yrs., whereas in those aged 40-45 yrs., the differences were non-significant but still inclined in favor of ICSI.
This study favors the use of ICSI in the older IVF population in order to increase both the fertilization rate and the number of top quality embryos that result per IVF cycle. Further studies are needed to establish our observations and use ICSI as the preferred approach to overcome egg sperm abnormal interactions related to advanced maternal age.
Long‐term elevated nitrogen (N) input from anthropogenic sources may cause soil acidification and decrease crop yield, yet the response of the belowground microbial community to long‐term N input ...alone or in combination with phosphorus (P) and potassium (K) is poorly understood. We explored the effect of long‐term N and NPK fertilization on soil bacterial diversity and community composition using meta‐analysis of a global dataset. Nitrogen fertilization decreased soil pH, and increased soil organic carbon (C) and available N contents. Bacterial taxonomic diversity was decreased by N fertilization alone, but was increased by NPK fertilization. The effect of N fertilization on bacterial diversity varied with soil texture and water management, but was independent of crop type or N application rate. Changes in bacterial diversity were positively related to both soil pH and organic C content under N fertilization alone, but only to soil organic C under NPK fertilization. Microbial biomass C decreased with decreasing bacterial diversity under long‐term N fertilization. Nitrogen fertilization increased the relative abundance of Proteobacteria and Actinobacteria, but reduced the abundance of Acidobacteria, consistent with the general life history strategy theory for bacteria. The positive correlation between N application rate and the relative abundance of Actinobacteria indicates that increased N availability favored the growth of Actinobacteria. This first global analysis of long‐term N and NPK fertilization that differentially affects bacterial diversity and community composition provides a reference for nutrient management strategies for maintaining belowground microbial diversity in agro‐ecosystems worldwide.
This study explored the effects of long‐term N and NPK fertilization on soil bacterial community in agro‐ecosystems using a meta‐analysis of datasets across the globe. The long‐term N fertilization significantly decreased soil bacterial diversity, changed bacterial community composition, and favored the growth of Actinobacteria and Proteobacteria over Acidobacteria. The negative effect of N fertilization on bacterial diversity disappeared when N is coapplied with P and K. This study represents an important step forward for understanding the connection between elevated nutrient inputs, shifts in soil microbial communities, and altered ecosystem functioning.
Ovarian follicle steroidogenesis associated with embryo quality results in a successful pregnancy. Each follicle consists of an oocyte surrounded by granulosa cells, which secrete several steroid and ...peptide hormones. Follicles harvested from women who conceived after assisted reproductive therapy (ART) had significantly higher estradiol levels in follicular fluids than the follicles from women who failed to conceive after ART. The higher follicular estradiol levels correlate well with successful fertilization following ART. Mitochondria are the central sites for steroid hormone biosynthesis. The first and rate-limiting step in the biosynthesis of steroid hormones occurs in the mitochondria of granulosa cells. In the present study, we hypothesized that the mitochondria in granulosa cells are critical for maintaining oocyte quality and fertility capacity. This study aims to clarify the relationship between mitochondrial function and granulosa cell steroidogenesis, and the relationship between hormone levels and fertility capacity. Sera, follicular fluids and granulosa cells were obtained from individuals undergoing IVF-ET treatment. The oocyte numbers, oocyte quality, fertilization rate, and pregnancy rate were also recorded. The patients who provided the granulosa cells were further classified into four groups: endometriosis, ovarian endometrioma, endometriosis without ovarian endometrioma, and polycystic ovary syndrome (PCOS); patients with other female factor infertility and male factor infertility were used as controls. We measured the levels of estradiol (E2) by radioimmunoassay. Concurrently, we analyzed the mitochondrial mass and membrane potential, and apoptosis by flow cytometry using nonyl acridine orange, TMRE, Annexin V-FITC and PI. Mitochondrial morphology was visualized by transfection with pLV-mitoDsRed. In addition, we assessed the protein levels of steroidogenic enzymes, steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) by Western blot. The results showed significantly decreased serum E2 and follicular E2 levels, and decreased IVF outcomes, in the patients with endometriosis. Reduced mitochondrial mass and decreased mitochondrial membrane potential were correlated with lower E2. Furthermore, a significant decrease in StAR and 3β-HSD was found in patients with ovarian endometrioma. The enzyme levels of StAR and 3β-HSD were highly correlated with E2 levels. Finally, elevated cumulus cell apoptosis was found in the patient group with ovarian endometrioma and PCOS. In conclusion, mitochondrial dysfunction of human granulosa cells may contribute to the decline of steroidogenesis, decreased fertilization rate, oocyte maturation rate, and oocyte quality, and it can ultimately jeopardize fertility.
Mild stimulation for in vitro fertilization Nargund, Geeta; Datta, Adrija Kumar; Fauser, Bart C.J.M.
Fertility and sterility,
October 2017, 2017-10-00, 20171001, Letnik:
108, Številka:
4
Journal Article
Recenzirano
Odprti dostop
It has been proven that the use of high gonadotropin dose does not necessarily improve the final outcome of IVF. Mild ovarian stimulation is based on the principle of optimal utilization of competent ...oocytes/embryos and endometrial receptivity. There is growing evidence that the pregnancy or live birth rates with mild-stimulation protocols are comparable to those with conventional IVF; the cumulative pregnancy outcome has been shown to be no different, despite having fewer numbers of oocytes or embryos available with milder ovarian stimulation. Although equally effective, mild-stimulation IVF is associated with a greater safety profile, in terms of the incidence of ovarian hyperstimulation syndrome and venous thromboembolism. It is also found to be better tolerated by patients and less expensive. Emerging research evidence may lead to widespread acceptance of mild IVF, by both patients and IVF providers, and make IVF more accessible to women and couples worldwide.
The advent of genome editing tools like CRISPR/Cas has substantially increased the number of genetically engineered mouse models in recent years. In support of refinement and reduction, sperm ...cryopreservation is advantageous compared to embryo freezing for archiving and distribution of such mouse models. The in vitro fertilization using cryopreserved sperm from the most widely used C57BL/6 strain has become highly efficient in recent years due to several improvements of the procedure. However, purchase of the necessary media for routine application of the current protocol poses a constant burden on budgetary constraints. In-house media preparation, instead, is complex and requires quality control of each batch. Here, we describe a cost-effective and easily adaptable approach for in vitro fertilization using cryopreserved C57BL/6 sperm. This is mainly achieved by modification of an affordable commercial fertilization medium and a step-by-step description of all other necessary reagents. Large-scale comparison of fertilization rates from independent lines of genetically engineered C57BL/6 mice upon cryopreservation and in vitro fertilization with our approach demonstrated equal or significantly superior fertilization rates to current protocols. Our novel SEcuRe (Simple Economical set-up for Rederivation) method provides an affordable, easily adaptable and harmonized protocol for highly efficient rederivation using cryopreserved C57BL/6 sperm for a broad application of colony management in the sense of the 3Rs.
Although in vitro fertilization has been associated with an increased risk for hypertensive disorders of pregnancy, the association of risk with in vitro fertilization treatment parameters is ...unclear.
To evaluate risk for hypertensive disorders of pregnancy by maternal fertility status and in vitro fertilization treatment parameters.
Women in 8 states who underwent in vitro fertilization resulting in a live birth during 2004–2013 were linked to their infant’s birth certificates. A 10:1 sample of births from non–in vitro fertilization deliveries were selected for comparison. Those with an indication of infertility treatment on the birth certificate were categorized as subfertile and omitted from the study population; all others were categorized as fertile. The in vitro fertilization pregnancies were additionally categorized by oocyte source (autologous versus donor) and embryo state (fresh versus thawed). Both the fertile and in vitro fertilization births were limited to singletons only, and the in vitro fertilization pregnancies were limited to those using partner sperm. Hypertensive disorders of pregnancy (including gestational hypertension and preeclampsia) were identified from the birth certificate, modeled using logistic regression, and reported as adjusted odds ratios and 95% confidence intervals. For analyses of in vitro fertilization pregnancies from autologous oocytes–fresh embryos, the reference group was fertile women (subgroup analysis 1). For analyses within the in vitro fertilization group, the reference group was autologous oocytes–fresh embryos (subgroup analysis 2).
The study population included 1,465,893 pregnancies (1,382,311 births to fertile women and 83,582 births to in vitro fertilization–treated women). Compared to fertile women, in vitro fertilization–treated women with autologous–fresh cycles were not at increased risk for hypertensive disorders of pregnancy (adjusted odds ratio, 1.04; 95% confidence interval, 0.99, 1.08). Among in vitro fertilization births (subgroup analysis 2), the risk for hypertensive disorders of pregnancy was increased for the autologous–thawed (adjusted odds ratio, 1.30; 95% confidence interval, 1.20, 1.40); donor–fresh (adjusted oddds ratio, 1.92; 95% confidence interval, 1.71, 2.15); and donor–thawed (adjusted odds ratio, 1.70; 95% confidence interval, 1.47, 1.96) groups. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results. When stratified by <34 weeks (early-onset hypertensive disorders of pregnancy) versus ≥34 weeks (late-onset hypertensive disorders of pregnancy), only the donor–fresh group had an increased risk of early-onset hypertensive disorders of pregnancy, but the risks for all other oocyte source–embryo state groups compared to autologous–fresh were increased for late-onset hypertensive disorders of pregnancy.
The risk for hypertensive disorders of pregnancy is increased for in vitro fertilization–treated women in pregnancies conceived via frozen embryo transfer (with both autologous or donor oocyte) and fresh donor oocyte embryo transfer. No increase in risk was seen with autologous oocyte-fresh embryo transfers in vitro fertilization cycles. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results.
Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced ...maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.
In contrast to the impact of elevated progesterone on endometrial receptivity, the data on whether increased progesterone levels affects the quality of embryos is still limited. This study ...retrospectively enrolled 4,236 fresh in vitro fertilization (IVF) cycles and sought to determine whether increased progesterone is associated with adverse outcomes with regard to top quality embryos (TQE). The results showed that the TQE rate significantly correlated with progesterone levels on the day of human chorionic gonadotropin (hCG) trigger (P = 0.009). Multivariate linear regression analysis of factors related to the TQE rate, in conventional IVF cycles, showed that the TQE rate was negatively associated with progesterone concentration on the day of hCG (OR was -1.658, 95% CI: -2.806 to -0.510, P = 0.005). When the serum progesterone level was within the interval 2.0-2.5 ng/ml, the TQE rate was significantly lower (P <0.05) than when the progesterone level was < 1.0 ng/ml; similar results were obtained for serum progesterone levels >2.5 ng/ml. Then, we choose a progesterone level at 1.5ng/ml, 2.0 ng/ml and 2.5 ng/ml as cut-off points to verify this result. We found that the TQE rate was significantly different (P <0.05) between serum progesterone levels < 2.0 ng/ml and >2.0 ng/ml. In conclusion, the results of this study clearly demonstrated a negative effect of elevated progesterone levels on the day of hCG trigger, on TQE rate, regardless of the basal FSH, the total gonadotropin, the age of the woman, or the time of ovarian stimulation. These data demonstrate that elevated progesterone levels (>2.0 ng/ml) before oocyte maturation were consistently detrimental to the oocyte.
Objective To evaluate the correlation between total gonadotropin dose and live birth rate. Design Retrospective analysis. Setting Not applicable. Patient(s) A total of 658,519 fresh autologous cycles ...of in vitro fertilization (IVF) reported to the Society for Assisted Reproductive Technology from 2004 to 2012. Intervention(s) None. Main Outcome Measure(s) Logistic regression models were fitted to live birth rates with the use of categorized values for total FSH dose and number of oocytes retrieved as the primary predictor variables. To reduce the effect of the most significant confounders that may lead physicians to prescribe higher doses of FSH, additional analyses were performed limited to good-prognosis patients (<35 years of age, body mass index <30 kg/m2 , and no diagnosis of diminished ovarian reserve, endometriosis, or ovulatory disorder) and including duration of gonadotropin treatment. Result(s) Live birth rate significantly decreased with increasing FSH dose, regardless of the number of oocytes retrieved. The statistically significant decrease in live birth rate with increasing FSH dose remained in patients with good prognosis, and regardless of female age, except for women aged ≥35 years with 1–5 oocytes retrieved. Conclusion(s) This analysis suggests that physicians may wish to avoid prescribing a high dose of FSH. However, the results of this study do not justify the use of minimal-stimulation or natural-cycle IVF.
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