The impact of difficult embryo transfer on the success of IVF: a systematic review and meta-analysis.

The procedure of embryo transfer (ET) must be as gentle as possible since any traumatism may cause uterine contractility that interferes with the implantation. However, this ideal conduct is not always possible, and additional measures may be necessary (difficult ET). Different studies have evaluated the impact of difficult ET on the clinical pregnancy rate (CPR), but results were not univocal. The present systematic review and meta-analysis was aimed to provide a precise estimate of the possible detrimental effects of difficult ET on CPR. The study protocol was registered online (PROSPERO number: CRD42023387197). An electronic database search was performed to identify articles published until September 2022. The primary outcome was CPR. Fifteen studies fulfilled the inclusion criteria. Difficult ET significantly reduced the CPR (OR 0.70; 95%CI: 0.64-0.76; p < 0.0001. All pre-planned subgroup analyses according to study design (retrospective vs prospective studies), historical period (studies published before and after 2010), type of catheter, frequency of difficult cases (> or < 19%) and pregnancy rate (> or < 38%) confirmed the significant association. Difficult ET is associated with a significant reduction of CPR. Further studies are warranted to understand how to prevent or manage this common clinical situation.

Prevalence and clinical effect of caesarean scar defects in women undergoing IVF.

RESEARCH QUESTION: How common are caesarean scar defects (isthmocele) among patients who have had previous caesarean delivery undergoing IVF for secondary infertility? Does the presence of isthmocele affect the chances of success of IVF? DESIGN: In this cohort study, women referred to an Italian public assisted reproduction centre between January 2016 and April 2021 were retrospectively reviewed. Women with a history of caesarean delivery and an indication for IVF were selected. On the basis of the local policy, all patients with a history of caesarean section underwent saline contrast sonography (SCS). Sonographic evaluation was standardized. RESULTS: One hundred and forty-four women were eligible, of whom 22 declined SCS and eight decided to delay pregnancy seeking. Overall, 114 women were available for data analysis. Seventy-six women were diagnosed with caesarean scar defects, corresponding to a prevalence of 67% (95% CI 58 to 75%). Baseline characteristics of women with and without isthmocele were similar. Conversely, the clinical pregnancy rate (adjusted OR 0.31, 95% CI 0.13 to 0.72) and live birth rate (adjusted OR 038, 95% CI 0.17 to 0.86) were significantly lower among affected women. No associations between specific sonographic defect characteristics and IVF outcome could be identified. CONCLUSIONS: Caesarean scar defects are common among women with a history of caesarean section requiring IVF. The presence of these lesions may reduce the chance of success of the procedure.

Satisfaction and usability of the recombinant chorionic gonadotropin prefilled pen: a survey in Italy.

BACKGROUND: Due to high purity, recombinant human chorionic gonadotropin (hCG) is suitable for subcutaneous injection, and hence for self-administration, in assisted reproduction. To increase usability and reduce the risk of dosing errors, a prefilled pen was produced. We investigated the ease of administration and satisfaction with the product amongst patients and healthcare professionals. METHODS: A survey was conducted amongst women with infertility who underwent in vitro fertilization treatments with recombinant hCG to trigger ovulation in various clinics in Italy. RESULTS: A total of 276 Italian women were interviewed. The median score of preference for the prefilled pen in comparison with hCG powder to be reconstituted in the solvent was rated as 9 (range 8-10), and 125 women answered that the prefilled pen had major advantages. Reasons for preference of the prefilled pen were linked to ease of use and safety: avoidance of dosage mistakes and of concern of such, ease of administration, certainty that the drug is correctly taken, safe administration and no anxiety. The procedure for recombinant hCG administration through the prefilled pen was judged as easy by 80% of respondents, with a median score of 9 (range 8-10) for easiness on a 1-10 scale. Out of 276 respondents, 249 (90%) had no problem with the injection. CONCLUSION: Overall, the respondents reported a favourable perception of the prefilled pen with hCG, which was reported to be easy to use and perceived to prevent dosage mistakes.

Safety of in-vitro fertilization in women with endometriosis.

Management of women with endometriosis in general is complex. It requires a multidisciplinary and tailored approach. The time of in-vitro fertilization (IVF) may be particularly complicated because women with the disease face peculiar additional risks. In particular, oocytes retrieval may be more difficult and women with endometriomas are exposed to a low but consistent risk of infection and ovarian abscess development. There are also concerns regarding progression of deep invasive peritoneal lesions and misdiagnosis of an occult early ovarian cancer. However, evidence on these latter points is more controversial. Taken together, this body evidence is generally reassuring and does not justify prophylactic surgery prior to IVF to shrink these risks. However, given the uncertainties, women with endometriosis must be informed in depth of these peculiar additional risks.

The impact of endometrioma size on ovarian responsiveness.

RESEARCH QUESTION: Available evidence shows that the presence of ovarian endometriomas does not interfere with the ovarian response to ovarian stimulation. However, the mean size of the endometriomas in these studies is generally small, and two recent investigations suggested that follicular development could be impaired when focusing on larger endometriomas. However, these studies could not identify a clear threshold above which endometriomas could become detrimental. DESIGN: To identify this threshold, the study retrospectively selected women without a history of surgery for ovarian cysts who underwent IVF in the presence of unilateral endometriomas with a mean diameter between 20 and 49 mm. Selected women were divided into three categories of endometrioma size: 20-29 mm (group 1, n = 23), 30-39 mm (group 2, n = 2323), and 40-49 mm (group 3, n = 2321). Recruitment for each category was censored at about 21 women to ensure equal statistical power for each group. RESULTS: The response to ovarian stimulation was equal or superior in the affected gonads in eight women (35%, 95% confidence interval [CI] 16-57%), seven women (30%, 95% CI 13-53%) and two women (10%, 95% CI 2-30%) in groups 1, 2 and 3, respectively. The median (interquartile range) number of developed follicles in the affected and intact ovaries was 6 (3-7) and 5 (4-9) in group 1 (P = 0.21), 4 (1-6) and 4 (3-7) in group 2 (P = 0.08), 5 (3-7), and 7 (4-8) in group 3 (P = 0.01), respectively. CONCLUSIONS: The threshold to be used to distinguish between endometriomas that might and might not interfere with ovarian response is 4 cm in diameter.

Fertility in female cancer survivors: a systematic review and meta-analysis.

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 < 0.00001 (two studies); brain cancer (HR 0.61, 95% CI 0.51 to 0.72; I2 = 14%; P < 0.00001 (three studies); RR 0.62, 95% CI 0.42 to 0.91 (one study); RaR 0.44, 95% CI 0.33 to 0.60; I2 = 95%; P < 0.00001 (four studies); OR 0.49, 95% CI 0.40 to 0.60 (one study); and kidney cancer (RR 0.66, 95% CI 0.43 to 0.98 (one study); RaR 0.69, 95% CI 0.61 to 0.78 (one study). Reproductive chances in women survivors of non-Hodgkin's lymphoma, melanoma and thyroid cancer were unaffected. Women with a history of bone, breast, brain or kidney cancer have reduced chances of childbirth. Thyroid cancer, melanoma and non-Hodgkin's lymphoma survivors can be reassured.

Oocyte quality in women with thalassaemia major: insights from IVF cycles.

BACKGROUND: Women with thalassaemia major typically experience hypogonadotropic hypogonadism because of the toxic effects of iron overload on the anterior pituitary. Moreover, in affected women, serum anti-Mullerian hormone (AMH) and antral follicle count (AFC) are also shown to be reduced, suggesting that the peripheral excess of iron could also harm the ovarian reserve. To date, the detrimental effects of the disease on oocyte quality have not been investigated. MATERIALS AND METHODS: Women with thalassaemia major who underwent in vitro fertilization (IVF) cycles were retrospectively identified over a 9 years period. They were matched (with a 1:5 ratio) by study period and age to a control group of infertile women undergoing IVF. Embriological variables were compared between the two groups. The primary outcome was the rate of top quality embryos. RESULTS: Twenty-one women with thalassaemia major (exposed group) and 105 controls (unexposed group) were ultimately included. Serum AMH was 0.6 [0.2-1.8] and 1.5 [0.7-3.5] ng/ml, respectively (p = 0.05). AFC was 4 (1-7.5) and 11 (5.5-16), respectively (p < 0.001). The total dose of gonadotropins used was higher in exposed women but the number of retrieved oocytes and oocytes used did not differ. The fertilization rate was higher in exposed compared to unexposed women, being 100% (76-100%) and 75% (50-100%). respectively (p = 0.03). The cleavage rate was also higher, being 75% (39-100%) and 50% (29-64%), respectively (p = 0.04). In contrast, the rate of top quality embryos did not differ, being 20% (0-76%) and 25% (5-50%), respectively (p = 0.98). CONCLUSIONS: Despite lower ovarian reserve, oocyte quality is not significantly affected in women with thalassaemia major.

Liver and Cardiovascular Damage in Patients With Lean Nonalcoholic Fatty Liver Disease, and Association With Visceral Obesity.

BACKGROUND & AIMS: Lean nonalcoholic fatty liver disease (NAFLD) is defined as NAFLD that develops in patients with a body mass index (BMI) less than 25 kg/m2. We investigated the differences between lean NAFLD and NAFLD in overweight and obese persons, factors associated with the severity of liver and cardiovascular disease, and the effects of visceral obesity. METHODS: We performed a retrospective cohort study of 669 consecutive patients with biopsy-proven NAFLD seen at 3 liver centers in Italy. We collected anthropometric, clinical, and biochemical data, as well as information on carotid atherosclerosis (artery intima-media thickness and plaque), liver histology (nonalcoholic steatohepatitis [NASH] and fibrosis), insulin resistance, and diabetes. Overweight was defined as a BMI of 25 to 29.9 kg/m2, and obese was defined as a BMI of 30 kg/m2 or greater. Patients were assigned to groups based on waist circumference, a marker of visceral obesity (low: men, <94 cm, women <80 cm; medium: men, 94-102 cm, women 80-88 cm; or high: men >102 cm, women >88 cm). DNA samples were analyzed for the rs738409 C>G (I148M in PNPLA3), the rs58542926 C>T (E167K in TM6SF2), and single-nucleotide polymorphisms. Variables in men and women were analyzed using chi-squared analysis and the Mann-Whitney or Kruskal-Wallis tests. Multiple linear or logistic regression analyses were adjusted for all the variables of clinical relevance or statistically significant at univariate analyses. The primary outcome was the difference in liver and cardiovascular disease between lean NAFLD and NAFLD in overweight and obese persons. Secondary outcomes were effects of visceral obesity, based on waist circumference, on hepatic, vascular, and metabolic features. RESULTS: Significantly lower proportions of patients with lean NAFLD (143 patients; 43 women; mean age, 46 ± 13 y) had hypertension (P = .001), diabetes (P = .0001), and metabolic syndrome (P = .0001) than overweight or obese patients with NAFLD (526 patients; 149 women; mean age, 49 ± 12 y). Significantly lower proportions of patients with lean NAFLD had NASH (17% vs 40% of obese or overweight patients with NAFLD; P = .0001), fibrosis of F2 or higher (17% vs 42%; P = .0001), or carotid plaques (27% vs 39%; P = .03). Patients with lean NAFLD had significantly thinner carotid intima-media (0.74 ± 0.1 mm) than obese or overweight patients with NAFLD (0.84 ± 0.3 mm; P = .0001). There was no significant difference in the proportions of patients with rs738409 C>G in PNPLA3, but a significantly greater proportion of patients with lean NAFLD carried rs58542926 C>T in TM6SF2 (4%) than obese or overweight individuals with NAFLD (0.3%; P = .001). Of the 143 patients with lean NAFLD, 27 had grade 3 steatosis, 24 had a lobular inflammation score greater than 2, 10 had a ballooning score of 2, and 25 had a fibrosis score of 2 or higher. In patients with lean NAFLD, the only variable associated independently with NASH and a fibrosis score of 2 or higher was rs738409 C>G in PNPLA3. Patients with lean NAFLD and a medium waist circumference had a significantly higher risk of diabetes (odds ratio, 11; 95% confidence interval [CI], 1.2-106; P = .03) than overweight or obese patients with a similar waist circumference (odds ratio, 1.3; 95% CI, 0.4-4.2; P = .6). Lean and overweight or obese patients with high waist circumferences had significant increases in risk compared with patients with low and medium circumference and diabetes, hypertension, and fibrosis scores of 2 or higher. CONCLUSIONS: In a retrospective study of patients with lean NAFLD vs obese or overweight persons with NAFLD, we found 20% of patients with lean NAFLD to have NASH, fibrosis scores of 2 or higher, and carotid atherosclerosis. Lean patients with rs738409 C>G in PNPLA3 should be monitored for liver disease progression; studies including large series of patients with lean NAFLD will clarify the possible role of TM6SF2 polymorphisms.