Vitamin and Carotenoid Intake and Outcomes of In Vitro Fertilization in Women Referring to an Italian Fertility Service: A Cross-Sectional Analysis of a Prospective Cohort Study.

BACKGROUND: Nutrition may impact reproductive health and fertility potential. The role of dietary antioxidants in affecting conception and birth outcomes is a topic of emerging interest. METHODS: This cross-sectional analysis from a prospective cohort study aims to explore the relationship between the intake of antioxidants, vitamins, and carotenoids and the outcomes of assisted reproduction techniques. Information on the socio-demographic characteristics, health histories, lifestyle habits, and diet information of subfertile couples referred to a fertility center was obtained. RESULTS: A total of 494 women were enrolled. According to the four IVF outcomes considered, 95% of women achieved good quality oocytes, 87% achieved embryo transfer, 32.0% achieved clinical pregnancies, and 24.5% achieved pregnancy at term. Associations were found between age and the number of good quality oocytes (p = 0.02). A moderate level of physical activity in the prior 5 years was associated with a better rate of achieving clinical pregnancy (p = 0.03). Smoking habits, alcohol intake, and caffeine consumption did not show associations with any outcome. No associations were found, even after accounting for potential confounders, with the intake of vitamins C, D, E, and α-carotene, ß-carotene, beta-cryptoxanthin, lutein, and folate. CONCLUSION: Further research is needed to understand how antioxidant intake may have a role in modulating fertility.

The impact of small and asymptomatic intramural and subserosal fibroids on female fertility: a case-control study.

STUDY QUESTION: Do small and asymptomatic intramural and subserosal uterine fibroids affect female fertility? SUMMARY ANSWER: Small and asymptomatic fibroids that do not encroach the endometrial cavity appear to not markedly affect female fertility. WHAT IS KNOWN ALREADY: The available evidence on uterine fibroids and fertility is limited. Most information has been obtained in IVF settings by comparing the success in women affected and not affected by fibroids. These studies have shown a detrimental effect of submucosal and possibly intramural fibroids. However, this study design provides information only on embryo implantation, not on female fertility in general. STUDY DESIGN SIZE DURATION: A retrospective observational case-control study on 200 women whose partner was diagnosed with severe male infertility and 200 women with unexplained infertility was conducted. If the null hypothesis (that fibroids do not affect fertility) is valid, one would expect a similar prevalence of fibroids in the two study groups. Conversely, if fibroids do impact fertility, one would expect a higher prevalence among women with unexplained infertility. The study was carried out at the Infertility Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico covering a 5-year period between January 2014 and June 2020. PARTICIPANTS/MATERIALS SETTING METHODS: We retrospectively recruited women seeking pregnancy whose partner was repeatedly documented to have a sperm concentration below 1 million/ml and matched them by age and study period to a group of women with unexplained infertility. The latter group of women was considered as a case group (infertile subjects), while the former group of women was considered as a control group (reflecting the general female population). Women with fibroids could be included in both study groups; only those with submucosal lesions were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Fibroids were diagnosed in 31 women (16%) with unexplained infertility and in 32 women (16%) with severe male factor infertility. The adjusted odds ratio of carrying fibroids in women with unexplained infertility was 0.91 (95% CI: 0.52-1.58). Subgroup analyses according to number, dimension and location of fibroids failed to highlight an increased risk of infertility in any group. LIMITATIONS REASONS FOR CAUTION: This is a retrospective study and some inaccuracies in fibroids detection cannot be ruled out. Moreover, the relatively small sample size hampers robust subgroup analyses. Even though we excluded women with patent causes of infertility, some women with specific causes of infertility could have been included among controls (yet are expected to account for <10% of the group). WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that small fibroids that do not encroach the endometrial cavity do not markedly affect female fertility. This information is clinically relevant when counseling infertile women with small fibroids and an otherwise unremarkable diagnostic work-up. Surgery may still be considered but only in selected cases. STUDY FUNDING/COMPETING INTERESTS: This study was partially funded by Italian Ministry of Health: current research IRCCS. E.S. reports grants from Ferring, grants and personal fees from Merck, and grants and personal fees from Theramex outside the submitted work. All the other authors do not have any competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

The impact of endometriosis on IVF efficacy: qualitative and quantitative assessment of ovarian response and embryo development.

RESEARCH QUESTION: The detrimental effects of endometriosis on IVF success are well known, but the underlying mechanisms are still uncertain. The objective of this study was to investigate the possible detrimental effects of the disease on ovarian response and embryo development. DESIGN: IVF cycles performed in the authors' unit between 2014 and 2020 were retrospectively reviewed. Women with a good ovarian reserve who underwent their first IVF cycle were included. A total of 248 women with endometriosis were identified and matched to 248 women without the disease, according to age, type of stimulation, anti-Müllerian hormone concentration and study period. The primary outcome was the number of women without good-quality embryos. Secondary outcomes included the rate of unexpected poor response (retrieval of ≤3 oocytes), the cumulative clinical pregnancy rate and the cumulative live birth rate. RESULTS: The number of women without good-quality embryos did not differ between women with endometriosis (exposed group) and those without it (unexposed group). The adjusted odds ratio was 0.85 (95% CI 0.51-1.44, P = 0.56). The clinical pregnancy rate and the live birth rate were also similar. Conversely, the rate of unexpected poor response was higher among women with endometriosis (23% versus 13%, P = 0.005). CONCLUSIONS: Overall, endometriosis does not markedly affect folliculogenesis and embryo development in the context of IVF. Only an increased risk of unexpected poor response emerged.

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.

Decidualization of endometriosis in a cohort of IVF-mediated pregnancies.

Decidualization is the process of endometrial change in pregnancy, a phenomenon that can involve also ovarian endometriomas. However, the frequency of this event remains unknown. In addition, there is no evidence on the decidualization of deep invasive endometriosis (DIE). To shed more light on this issue, we prospectively recruited women with ovarian endometriomas or DIE who underwent IVF. They were subsequently excluded if they did not become pregnant or if they had a miscarriage. The evaluation was repeated in five time points during pregnancy and post-partum. The primary outcome was the rate of decidualized endometriomas at 11-13 weeks' gestation. Data from 45 endometriomas and 15 nodules were available for data analyses. At the 11-13 weeks' ultrasound, endometriomas' decidualization was observed in seven cases, corresponding to 16% (95% CI 8-29%). Subsequent assessments in pregnancy failed to identify any additional case. DIE also underwent significant changes during pregnancy. At the 11-13 weeks' ultrasound, lesions were increased in size and more vascularized. In conclusion, decidualization of ovarian endometriomas in IVF pregnancies is not rare. DIE may also undergo decidualization, but further evidence is needed for a robust and shared definition of this process.

Antioxidant Vitamins and Carotenoids Intake and the Association With Poor Semen Quality: A Cross-Sectional Analysis of Men Referring to an Italian Fertility Clinic.

Several studies suggested that male's diet affects fertility. This cross-sectional analysis from a prospective cohort study aims to explore the relation between antioxidants intake and sperm parameters in sub-fertile couples referring to a Fertility center. Socio-demographic characteristics, health history, lifestyle habits, and diet information were obtained. A semen sample was analyzed to proceed with assisted reproduction. Three hundred and twenty-three men were enrolled: 19.1% had semen volume (SV) < 1.5 mL, 31.4% sperm concentration (SC) < 15.0 mil/mL, 26.8% sperm motility < 32%, and 33.0% had total sperm count (TSC) < 39.0 mil. Higher levels of α-carotene were associated to lower risk of low SC [4th vs. 1st quartile, adjusted OR (aOR) 0.43, 95% CI 0.20-0.91) and low TSC (aOR 0.46, 95% CI 0.22-0.95). Higher intake of ß-carotene was inversely associated with risk of low TSC. Lycopene intake was associated with higher risk for these conditions (aOR 2.46, 95%CI 1.01-5.98, SC), and (aOR 3.11, 95%CI 1.29-7.50, TSC). Risk of low semen volume was lower in men with higher level of vitamin D intake (aOR 0.25, 95%CI 0.09-0.66)]. Further research, especially, well-designed randomized clinical trials (RCT), is needed to understand how diet modifications may have a role in modulating male fertility and fecundability.

Endometriosis and spontaneous hemoperitoneum in pregnancy: evaluation of the magnitude of the risk in women becoming pregnant via in vitro fertilization.

OBJECTIVE: To estimate the frequency of spontaneous hemoperitoneum in pregnancy (SHiP) in women with endometriosis achieving pregnancy with in vitro fertilization (IVF). DESIGN: Retrospective case series. SETTING: Referral academic assisted reproductive technology (ART) center. PATIENT(S): Three hundred and forty-eight women with a history of surgery for endometriosis and women with ovarian endometriomas or deep endometriotic nodules detected at basal transvaginal ultrasound performed before IVF cycle. INTERVENTION(S): Information obtained from patients' charts on basal characteristics, IVF cycle, and pregnancy outcomes, and binomial distribution model created to determine the 95% confidence interval (CI) of the proportion of SHiP. MAIN OUTCOME MEASURE(S): Rate of SHiP. RESULT(S): Overall, 362 pregnancies were included, among which 238 (66%) had a history of previous surgery for endometriosis and 231 (64%) had endometriosis detected at ultrasound (107 women, 30%, had both). Pregnancies were achieved after fresh and frozen cycles in 244 (67%) and 118 (33%) women, respectively. One case of SHiP was recorded, corresponding to a rate of 0.3%. CONCLUSION(S): In the general population of women with endometriosis undergoing IVF, SHiP is uncommon. Future studies should better identify the risk factors for SHiP to disentangle the subgroups of women at higher risk.

Pretreatment maternal lifestyle and outcomes of assisted reproduction: an Italian cohort study.

OBJECTIVE: We investigated whether lifestyle affects assisted reproduction technology (ART) outcomes. DESIGN: Cohort study. SETTING: Italian fertility unit. PARTICIPANTS: From September 2014 to December 2016, women from couples presenting for evaluation and eligible for ART were invited to participate. Information on alcohol intake, current smoking and leisure physical activity (PA) during the year before the interview was collected, using a structured questionnaire. We considered the ART outcomes of the cycle immediately following the interview. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was cumulative pregnancy rate per retrieval. Secondary measures were number of retrieved oocytes, embryo transfer and live birth. RESULTS: In 492 women undergoing an ART cycle, 427 (86.8%) underwent embryo transfer, 157 (31.9%) had at least one clinical pregnancy and 121 (24.6%) had live birth. The cumulative pregnancy rate per retrieval was 33.3% (95% CI 28.5% to 38.7%). In women in the third tertile of alcohol intake, adjusted relative risk was 0.97 (95% CI 0.87 to 1.08), 0.90 (95% CI 0.62 to 1.30) and 0.89 (95% CI 0.57 to 1.37) for embryo transfer, clinical pregnancy and live birth, respectively. The corresponding figures in women currently smoking more than 5 cigarettes/day were 1.00 (95% CI 0.88 to 1.16), 0.94 (95% CI 0.60 to 1.48) and 1.14 (95% CI 0.68 to 1.90), and in women with PA ≥5 hours/week were 0.93 (95% CI 0.79 to 1.08), 0.44 (95% CI 0.22 to 0.90) and 0.48 (95% CI 0.22 to 1.05), respectively. CONCLUSION: There were no significant differences in in vitro fertilisation outcomes among women who used alcohol or tobacco in the year prior to treatment. Conservatively, all women should be advised to limit substance abuse. Moreover, our study suggested that maintaining a moderate, but not high, level of PA could be beneficial.

Dietary Carbohydrate Intake, Dietary Glycemic Load and Outcomes of In Vitro Fertilization: Findings from an Observational Italian Cohort Study.

In recent decades, increasing attention has been paid to the influence of diet on reproductive health. Carbohydrates in diet affect glucose metabolism and multiple evidences showed the key role of insulin sensitivity in regulating female fertility. We designed a prospective cohort study to investigate the relation between dietary carbohydrate intake, glycemic load (GL) and the outcomes of assisted reproduction. A population of 494 female partners of couples referring to an Italian Fertility Center and eligible for in vitro fertilization (IVF) were enrolled in the study. On the day of the oocyte retrieval, information on their diet was obtained using a validated food frequency questionnaire (FFQ). We calculated the relative risk and 95% confidence interval of embryo transfer, clinical pregnancy and live birth according to the following dietary exposures: GL, glycemic index (GI) as well as the daily carbohydrate and fiber intake. A multiple regression model was used to account for the confounders. After adjusting for age, college degree, body mass index (BMI), leisure physical activity and previous assisted reproduction techniques (ART) cycles, no significant association was observed between the considered dietary exposures and the IVF outcomes. The roles of GL, carbohydrate intake and GI were assessed in strata of the cause of infertility and body mass index and no relation emerged in this further analysis. We found no clear association between the dietary carbohydrate quantity and quality and IVF outcomes in a cohort of infertile Italian women.

Fatty acids, food groups and semen variables in men referring to an Italian Fertility Clinic: Cross-sectional analysis of a prospective cohort study.

Diet has been suggested as a factor affecting sperm quality, both in healthy and infertile men. To study whether specific food groups and fatty acids (FA) intake were associated with sperm parameters of men from couples referring to an Italian Fertility Clinic, we conducted a cross-sectional analysis. A semen sample was collected and analysed before proceeding with assisted reproduction. To evaluate food groups and fatty acids intake, we used a questionnaire of food frequency. We calculated odds ratios (OR) and 95% confidence intervals (CI) for abnormal semen parameters. Among 323 men, 19% had semen volume (SV) <1.5 ml, 31% sperm concentration (SC) <15 mil/mL, 33% total sperm count (TSC) <39 mil and 27% sperm progressive motility <32%. Low SC was more frequent in men with higher saturated FA (SFA) and polyunsaturated FA (PUFA) intake. Better SC and TSC were related to higher monounsaturated FA (MUFA)/SFA ratio. Monounsaturated FA and linoleic/linolenic acid ratio were not related to any considered parameters. Low TSC was associated with low vegetable intake. In conclusion, normal sperm parameters were more frequent in men with low intake of SFA and PUFA, and high vegetable intake. Higher MUFA/SFA ratio was associated with better sperm quality parameters.

Reply: On the Reporting of Odds Ratios and Risk Ratios, Nutrients 2018, 10, 10.

In response to the letter of Pace and Multani, in general, we cannot disagree with their considerations about the use of odds ratios, risk ratios, and rate ratios. [...].

Maternal and Paternal Caffeine Intake and ART Outcomes in Couples Referring to an Italian Fertility Clinic: A Prospective Cohort.

Caffeine intake, a frequent lifestyle exposure, has a number of biological effects. We designed a cohort study to investigate the relation between lifestyle and assisted reproduction technique (ART) outcomes. From September 2014 to December 2016, 339 subfertile couples referring to an Italian fertility clinic and eligible for ART procedures were enrolled in our study. Sociodemographic characteristics, smoking, and usual alcohol and caffeine consumption in the year prior to ART were recorded. The mean age of participants was 36.6 ± 3.6 years in women and 39.4 ± 5.2 years in men. After oocytes retrieval, 293 (86.4%) underwent implantation, 110 (32.4%) achieved clinical pregnancy, and 82 (24.2%) live birth. Maternal age was the main determinant of ART outcome. In a model including women's age and college degree, smoking habits, calorie and alcohol intake for both partners, previous ART cycles, and partner's caffeine intake, we did not observe any association between caffeine intake and ART outcome. Using the first tertile of caffeine intake by women as a reference, the adjusted rate ratio (ARR) for live birth was 1.09 (95% confidence interval (CI) 0.79⁻1.50) in the second and 0.99 (95% CI 0.71⁻1.40) in the third tertiles. In conclusion, a moderate caffeine intake by women and men in the year prior to the ART procedure was not associated with negative ART outcomes.

Homocysteine pathway and in vitro fertilization outcome.

A prospective study investigating whether levels of the homocysteine pathway are associated with pregnancy rate in in vitro fertilization (IVF). Prior to initiate treatments, women gave a blood sample to test serum and red blood cell (RBC) folates, homocysteine and vitamin B12. The main outcome was cumulative clinical pregnancy rate according to basal levels of serum and RBC folates, homocysteine and vitamin B12. Two-hundred-nine women were selected, of whom 56 achieved a clinical pregnancy (27%). Median [interquartile range] levels of RBC and serum folate in women who did and did not become pregnant were 328 and 263 ng/ml (p = 0.018) and 13.6 and 9.4 ng/ml (p = 0.001), respectively. The adjusted ORs (95%CI) of pregnancy in women with RBC and serum folate concentrations in the upper tertile of the distributions were 2.6 (1.4-5.1) and 1.9 (1.0-3.7), respectively. Women undergoing IVF treatments with higher levels of folate have a higher chance of clinical pregnancy.

Folate, homocysteine and selected vitamins and minerals status in infertile women.

OBJECTIVES: Diet has been recognised as a crucial factor influencing fetal and maternal health. Adequate levels of substances such as homocysteine, folate and vitamin B12 have been associated with a higher rate of success in infertility treatments. Few data, however, are available on the average levels of micronutrients in the blood of reproductive-aged women, and specific values for adequate levels are not available. The aim of this cross-sectional study was to measure levels of folate, homocysteine and selected vitamins and minerals in women attending the infertility unit of an academic hospital for in vitro fertilisation (IVF). METHODS: Fasting venous blood samples were taken in the morning during routine screening before IVF in order to measure: serum folate, red blood cell (RBC) folate, total plasma homocysteine, vitamin B12, vitamin A, vitamin E, serum iron and serum ferritin. RESULTS: Among 269 women aged 37 ± 4 years, only 69% and 44% showed adequate levels of homocysteine and vitamin B12, respectively. Serum folate was appropriate in 78% of the study participants, but only a minority (12%) had a concentration of RBC folate regarded as optimal for the prevention of fetal neural tube defects. Serum levels of vitamin A, vitamin E, iron and ferritin were, however, appropriate in the vast majority of participants (>80%). CONCLUSION: Folate levels were largely inadequate among women attending an infertility clinic for IVF. Vitamin B12 levels were also found to be inadequate.

Serum Levels of 25-Hydroxyvitamin D and Time to Natural Pregnancy.

AIM: The aim of this study was to evaluate whether natural fertility is related to serum 25-hydroxyvitamin D (25-OH-vitamin D) levels. METHODS: A nested case-control study was designed from a prospective cohort of pregnant women undergoing first trimester screening for aneuploidies. Cases included women seeking pregnancy for 12-24 months. Controls were the subsequent age-matched women conceiving in less than 1 year. We excluded women aged ≥40 or <18 years, those assuming supplementary products that included vitamin D before or during pregnancy, those with irregular menstrual cycles or known causes of subfertility, those conceiving through assisted reproductive techniques or requiring ovarian stimulation and those who were overweight or obese. A quantitative detection of serum 25-OH-vitamin D and patients' interview were performed. RESULTS: Seventy-three cases and 73 matched controls were selected. The mean ± SD serum 25-OH-vitamin D was 21.2 ± 6.8 and 19.7 ± 7.3 ng/ml, respectively (p = 0.16). The number (%) of women with serum levels <20 ng/ml (vitamin D insufficiency) was 34 (47%) and 37 (51%), respectively (p = 0.73). The adjusted OR of longer time to pregnancy in women with vitamin D insufficiency was 0.84 (95% CI 0.42-1.66). CONCLUSIONS: Our study does not support a crucial role of 25-OH-vitamin D in natural fertility.

Serum anti-Müllerian hormone in subfertile women.

INTRODUCTION: The correlation between ovarian reserve and infertility remains unclear. Albeit poorly predictive of pregnancy success in in vitro fertilization cycles, serum anti-Müllerian hormone (AMH) has been acknowledged as a surrogate measure of ovarian reserve and is commonly evaluated in women seeking pregnancy. Disentangling whether low serum AMH affects natural fecundity is clinically important, as this information helps physicians in providing appropriate counseling to women and may impact on management strategies. MATERIAL AND METHODS: This was a nested case-control study from a prospective cohort of pregnant women undergoing first trimester screening for aneuploidies. Cases were subfertile women having tried to become pregnant for 12-24 months. Controls were subsequent age-matched fertile women. Inclusion criteria for both cases and controls were: (i) age > 18 years, (ii) natural conception, (iii) regular menstrual cycles (24-35 days). We used quantitative detection of serum AMH and interviews with the women. The main outcome measure was the proportion of women with serum AMH < 1.1 ng/mL. RESULTS: Seventy-six subfertile women and 76 matched fertile controls were selected. In the two study groups, there were 11 (15%) and 15 (20%) women with serum AMH < 1.1 ng/mL, respectively (p = 0.52). The crude odds ratio for subfertility in women with low serum AMH was 0.69 [95% confidence interval (CI) 0.29-1.62]. The adjusted odds ratio was 0.85 (95% CI 0.35-2.10). The median (interquartile range) serum concentration of AMH in subfertile and control women was 2.6 (range 1.6-4.0) and 2.8 (range 1.4-4.3) ng/mL, respectively (p = 0.91). CONCLUSIONS: Low serum AMH is not associated with female subfertility.

A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria.

STUDY QUESTION: Do the Bologna criteria for poor responders successfully identify women with poor IVF outcome? SUMMARY ANSWER: The Bologna criteria effectively identify a population with a uniformly low chance of success. WHAT IS ALREADY KNOWN: Women undergoing IVF who respond poorly to ovarian hyper-stimulation have a low chance of success. Even if improving IVF outcome in this population represents a main priority, the lack of a unique definition of the condition has hampered research in this area. To overcome this impediment, a recent expert meeting in Bologna proposed a new definition of poor responders ('Bologna criteria'). However, data supporting the relevance of this definition in clinical practice are scanty. STUDY DESIGN, SIZE, DURATION: Retrospective study of women undergoing IVF-ICSI between January 2010 and December 2012 in two independent infertility units. Women could be included if they fulfilled the definition of poor ovarian response (POR) according to Bologna criteria prior to initiation of the cycle. Women were included only for one cycle. The main outcome was the live birth rate per started cycle. The perspective of the cost analysis was the one of the health provider. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three-hundred sixty-two women from two independent Infertility Units were selected. A binomial distribution model was used to calculate the 95% CI of the rate of success. Characteristics of women who did and did not obtain a live birth were compared. A logistic regression model was used to adjust for confounders. The economic analysis included costs for pharmacological compounds and for the IVF procedure. The benefits were estimated on quality-adjusted life years (QALY). To develop the model, we used the local life-expectancy tables, we applied a 3% discount of life years gained and we used a 0.07 improvement in quality of life associated with parenthood. Sensitivity analyses were performed varying the improvement of the quality of life and including/excluding the male partner. The reference values for cost-effectiveness were the Italian and the local (Lombardy) gross domestic product (GDP) pro capita per year in the studied period and the upper and lower limits suggested by NICE. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 23 women had a live birth (6%, 95% CI: 4-9%), in line with the previous evidence. This proportion did not significantly differ in the different subgroups of poor responders. Positive predictive factors of success were previous deliveries (adjusted OR = 3.0, 95% CI: 1.1-8.7, P = 0.039) and previous chemotherapy (adjusted OR = 13.9, 95% CI: 2.5-77.2, P = 0.003). Age, serum AMH, serum FSH and antral follicle count were not significantly associated with live birth. The total cost per live birth was 87 748 Euros, corresponding to 49 919 Euros per QALY. This is above both the limits suggested by NICE for cost-effectiveness and the Italian and local GDP pro capita. Sensitivity analyses mainly support the robustness of the conclusion. LIMITATIONS, REASONS FOR CAUTION: We lack a control group and we cannot thus exclude that an alternative definition of poor responders may be equally if not more valid. Moreover, independent validations are warranted prior to concluding that IVF is not cost-effective. Women should thus not be denied treatment based on our findings. Noteworthy, there is also not yet a consensus on the most appropriate economic model to be used. WIDER IMPLICATIONS OF THE FINDINGS: We recommend the use of the Bologna criteria when designing future studies on poor responders. Large multi-centred international studies are now required to draw definite conclusions on the economic profile of IVF in this situation.