Search

Available evidence from IVF studies supports a detrimental effect of submucosal and intramural fibroids on embryo implantation. It is misleading, however, to infer evidence obtained in IVF settings to natural fertility. Therefore, a systematic review and meta-analysis was conducted on the effect of fibroids on natural fertility. Studies comparing fertile and infertile women, and those investigating whether the presence of fibroids was a risk factor, were reviewed, as well as studies comparing women with and without fibroids. The aim was also to establish whether the frequency of infertility differed between the two groups. Seven out of 11 selected studies did not aim to establish whether fibroids caused infertility but, rather, whether a history of infertility could be a risk factor for fibroids. A meta-analysis of the four remaining studies that concomitantly evaluated the presence of fibroids and infertility studies highlighted a common odds ratio of fibroids in subfertile women of 3.54 (95% CI 1.55 to 8.11). When focusing on the two most informative studies, i.e. the studies comparing time to pregnancy in women with and without fibroids, the common OR was 1.93 (95% CI 0.89 to 4.18). In conclusion, the association between fibroids and infertility has been insufficiently investigated. Epidemiological studies suggest, but do not demonstrate, that fibroids may interfere with natural fertility. Given the high prevalence of these lesions in women seeking pregnancy, further evidence is urgently needed.

Objective To investigate the impact of serum vitamin D level on in vitro fertilization (IVF) outcomes. Design Systematic review and meta-analysis. Setting Not applicable. Patients Infertile women undergoing conventional IVF or intracytoplasmic sperm injection (ICSI). Interventions Systematic search of PubMed, MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database, and Web of Science from inception until July 2019 with cross-checking of references from relevant articles in English. Vitamin D levels were categorized into three groups: deficient ( 30 ng/mL). Before starting the data extraction, we registered the review protocol in PROSPERO (CRD42019134258). Main Outcome Measures We consider clinical pregnancy rate (CPR), live birth rate (LBR), and/or ongoing pregnancy rate (OPR) as primary outcomes. Likewise, the miscarriage rate was considered as a secondary outcome. Results Primary analysis showed that women with a replete level of vitamin D had higher CPR and LBR/OPR compared to those with a deficient of insufficient level of vitamin D. However, sensitivity analysis led to non-significant differences between the comparators for CPR (odds ratio 0.71, 95% confidence interval 0.47−1.08, I2 = 61%) and OPR/LBR (odds ratio 0.78, 95% confidence interval 0.56−1.08], I2 = 61%). Also, for miscarriage a statistically different rate was not reached. Conclusion Serum vitamin D levels do not influence IVF outcomes in terms of CPR, LBR/OPR, and miscarriage rate. Future large cohort studies are warranted to determine whether the threshold of vitamin D affects reproductive outcomes. Currently, there is a lack of consensus between the appropriate vitamin D threshold to predict reproductive outcomes compared to the one established for bone health. PROSPERO Number CRD42019134258.

Data on the effects of cancer treatments on fertility are conflicting. The aim of the present systematic review and meta-analysis was to determine the chances of childbirth in women survivors of different types of cancer. PubMed, MEDLINE, Embase and Scopus were searched from database inception to 17 July 2019 for published cohort, case-control and cross-sectional studies that investigated the reproductive chances in women survivors of different cancer types. Random-effects models were used to pool childbirth hazard ratios, relative risks, rate ratios and odds ratios, and 95% confidence intervals were estimated; 18 eligible studies were identified. Childbirth chances were significantly reduced in women with a history of bone cancer (HR 0.86, 95% CI 0.77 to 0.97; I2 = 0%; P = 0.02 (two studies); RaR 0.76, 95% CI 0.61 to 0.95; I2 = 69%; P = 0.01 (two studies); breast cancer (HR 0.74, 95% CI 0.61 to 0.90 (one study); RaR 0.51, 95% CI 0.47 to 0.57; I2 = 0%; P

Controlled ovarian hyperstimulation (COH) determines an anticipation of endometrial maturation and a premature occurrence of the implantation window, as shown by histological, histochemical, and molecular studies and indirectly by clinical trials. There is growing agreement that in patients hyper-responding to COH and in those undergoing transfer at the blastocyst stage, deferring the transfer in a subsequent frozen cycle could increase pregnancy outcomes. For blastocysts, implantation after a fresh transfer may be limited as the implantation window is already closed while, in hyper-responders to COH, the anticipation magnitude could be more marked thus hampering implantation also for cleavage-stage embryos. Research should focus in depth on pregnancy outcomes and on the most suitable modality to prepare the endometrium for frozen transfers.

Research question What is the real prevalence of repeated implantation failure (RIF) and what reliable estimates can be given on the risk of false–positive diagnosis after two or three failed IVF attempts. Design A recent theoretical model suggested that commonly used definitions (two or three failed IVF attempts in good-prognosis couples) may expose couples to substantial odds of overdiagnosis and overtreatment. This model, however, was theoretical and based on unproven assumptions that the pregnancy rate in the non-RIF population was 30% and the prevalence of RIF was 10%. In the present study, we applied this model to real data to distinguish the real prevalence of RIF and to provide more reliable estimates on the risk of false–positive diagnosis after two or three failed IVF attempts. To this aim, we retrospectively selected 1221 good-prognosis couples and evaluated pregnancy rates up to the third cycle. Results The clinical pregnancy rate at first, second and third IVF cycle was 52%, 41% and 28%, respectively. A pregnancy rate of 61% was extrapolated in the non-RIF population and 15% among women who had experienced RIF. Therefore, the rate of false–positive diagnoses of RIF after two, three and six failed cycles would be 46%, 25%, and 2%, respectively. Conclusions Our analyses show that estimated prevalence of RIF is 15%. The frequently used definition of RIF based on three failed attempts (but not two) in good-prognosis couples seems justified. Physicians, however, should bear in mind that couples may be inappropriately labelled with this condition in one out of four cases.

The clinical management of women with deep peritoneal endometriosis remains controversial. The debate focuses mainly on the precise role of hormonal medical treatment and surgery and on the most suitable surgical technique to be used. In particular, considering the risks of second-line surgery, prevention of recurrences after first-line surgery is a priority in this context. Post-surgical medical therapy has been advocated to improve the effectiveness of surgery and prevent recurrences. However, adjuvant therapy, i.e. a short course of 3-6 months of hormonal therapy after surgery, has been proven to be of limited or no benefit for endometriosis in general and for deep peritoneal endometriosis in particular. On the other hand, two cohort studies suggest a beneficial effect of prolonged hormonal therapy after surgery for deep endometriosis. Even if this evidence is too weak to confidently advocate systematic administration of prolonged medical therapy after surgery, we argue in favour of this approach because of the strong association of deep endometriosis with other disease forms. In fact, women operated on for deep endometriosis may also face recurrences of endometriomas, superficial peritoneal lesions and pelvic pain in general. The demonstrated high effectiveness of prolonged postoperative therapy for the prevention of endometriomas' formation and dysmenorrhea recurrence should thus receive utmost consideration in the decision-making process.

This systematic review of the literature reports on the use and effectiveness of sperm banking programmes for cancer patients. Thirty studies with 11798 patients were included. The aggregated rate of use of cryopreserved semen was 8% (95% CI 8 to 9%). A statistically significant correlation emerged between the mean and median duration of follow-up and the rate of use (R(2) = 0.46; P = 0.03). The rate of patients discarding their frozen sample was reported in 11 studies. The aggregated rate was 16% (95% CI 15 to 17%). The rate of patients who used their frozen semen and achieved parenthood was reported in 19 papers. The aggregated rate was 49% (95% CI 44 to 53%). The rate of patients achieving parenthood with the use of frozen sperm is low and, from an economical perspective, the effectiveness of programmes of sperm banking might therefore be questioned. On the other hand, the low rate of patients discarding their frozen samples and the correlation between rate of use and duration of follow-up suggest that the calculated 8% rate of use may be an under-estimation and that cumulative rate of use may be substantially higher. Specific studies are, however, required to clarify this issue.

Evidence on the long-term impact of controlled ovarian hyperstimulation (COH) on thyroid function is scarce. To investigate this, we report on serum thyroid-stimulating hormone (TSH) modifications in euthyroid and hypothyroid women during COH and 3 months after the end of the stimulation cycle.Women who underwent in vitro fertilization (IVF) and who did not become pregnant were eligible. Cases were women with treated hypothyroidism and basal serum TSH2.5 mIU/L. Controls were euthyroid women matched to cases by age and basal serum TSH. Women could be included if serum TSH was available at 4 time points: prior to initiating COH (time 1); at the time of human chorionic gonadotropin (hCG) administration (time 2); 16 days after hCG administration (time 3); and 3 months after the end of the IVF cycle (time 4).Thirty-seven case-control pairs were included. Serum TSH at times 1, 2, 3, and 4 was 1.7 ± 0.6, 3.1 ± 1.4, 3.1 ± 1.3, and 2.7 ± 1.7 mIU/L, and 1.7 ± 0.6, 2.9 ± 1.0, 2.7 ± 1.0, and 1.9 ± 0.7 mIU/L among cases and controls, respectively. A statistically significant difference emerged at time 4 (P.001). In both groups, serum TSH was higher at time 4 compared to time 1. Serum TSH exceeded the recommended threshold of 2.5 mIU/L at time 4 in 51% of cases (95% confidence interval [CI], 35 to 68%) and in 16% of controls (95% CI, 4 to 28%) (P = .003).COH seems to have a long-term impact on TSH levels. The magnitude of this effect is particularly pronounced in hypothyroid women.

To evaluate the rate of euthyroid women encountering an elevation of serum TSH above the threshold of 2.5 mIU/L during controlled ovarian hyperstimulation (COH) for IVF.Six-month prospective cohort study on 175 consecutive euthyroid women undergoing their first IVF cycle. Serum TSH assessments were performed before COH, at the time of hCG administration and at +16 days after hCG administration. Women were eligible if serum TSH tested the month preceding the IVF cycle was 0.4-2.5 mIU/L. A history of thyroid disorders was an exclusion criterion.Serum concentrations of TSH at the three scheduled assessments were 1.5±0.5, 2.2±1.0 and 2.1±1.1 mIU/L, respectively. A statistically significant increase occurred between basal levels and levels at the time of hCG administration (p0.001). Afterwards, levels remained stable (p=0.49). Serum TSH at the time of hCG administration exceeded the threshold of 2.5 mIU/L in 61 subjects, corresponding to 35% (95% CI: 28-42%). At +16 days after hCG administration, this event was observed in 47 subjects (27%, 95% CI: 21-34%). Baseline characteristics of women who did and did not exceed the threshold were similar apart from basal serum TSH, which was higher in the former group. The OR was 7.6 (95%CI: 2.9-20.2) per mIU/L (p0.001). Cycle outcome and pregnancy rate were also similar.Serum TSH exceeds the threshold of 2.5 mIU/L during COH in one out of three women who are euthyroid prior to enter an IVF cycle. Further evidence is warranted to elucidate the clinical relevance of our findings.