Risk factors for monozygotic twinning after in vitro fertilization : a systematic review and meta-analysis

Objectives: To establish the risk factors for monozygotic twin (MZT) and monochorionic twin (MCT) pregnancies after in vitro fertilization (IVF). Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Women who achieved MZT and non-MZT pregnancies through IVF. Intervention(s): Systematic search of Medline from January 1995 to October 2018 with cross-checking of references from relevant articles in English. Main Outcome Measure(s): Possible risk factors for MZT or MCT pregnancies after IVF, comprising extended embryo culture, insemination method (conventional IVF and intracytoplasmic sperm injection [ICSI]), embryo biopsy for preimplantation genetic testing for aneuploidies or for monogenic/single-gene defects (PGT-A or PGT-M) programs, assisted hatching (AH), oocytes donation, female age, and embryo cryopreservation. Result(s): A total of 40 studies were included. Blastocyst transfer compared with cleavage-stage embryo transfer, and female age <35 years were associated with a statistically significant increase in the MZT and MCT pregnancy rate after IVF: (23 studies, OR 2.16, 95% CI, 1.74\u20132.68, I 2 =78%; 4 studies, OR 1.29; 95% CI, 1.03\u20131.62, I 2 =62%; and 3 studies, OR 1.90, 95% CI, 1.21\u20132.98, I 2 =59%; 2 studies, OR 2.34; 95% CI, 1.69\u20133.23, I 2 =0, respectively). Conventional IVF compared with ICSI and assisted hatching were associated with a statistically significantly increased risk of MZT pregnancy (9 studies, OR 1.19, 95% CI, 1.04\u20131.35, I 2 =0; 16 studies, OR 1.17, 95% CI, 1.09\u20131.27, I 2 =29%, respectively). Embryo biopsy for PGT-A or PGT-M, embryo cryopreservation, and oocytes donation were not associated with MZT pregnancies after IVF. Conclusion(s): Blastocyst transfer is associated with an increased risk of both MZT and MCT pregnancies after IVF. Further evidence is needed to clarify the impact of female age, insemination method and AH on the investigated outcomes

Oocyte retrieval difficulties in women with ovarian endometriomas

Research question: What are the frequency, characteristics and consequences of technical diffiiculties encountered by physicians when carrying out oocyte retrieval in women with ovarian endometriomas? Design: We prospectively recruited women undergoing IVF and compared technical difficulties between women with (n = 56) and without (n = 227) endometriomas. Results: In exposed women, the cyst had to be transfixed in eight cases (14%, 95% CI 7 to 25%) and accidental contamination of the follicular fluid with the endometrioma content was recorded in nine women (16%, 95% CI 8 to 27%). Moreover, follicular aspiration was more frequently incomplete (OR 3.6, 95% CI 1.4 to 9.6). In contrast, the retrievals were not deemed to be more technically difficult by the physicians and the rate of oocytes retrieved per developed follicle did not differ. No pelvic infections or cyst ruptures were recorded (0%, 95% CI 0 to 5%). Conclusions: Oocyte retrieval in women with ovarian endometriomas is more problematic but the magnitude of these increased difficulties is modest

Effect of vitamin D supplementation on assisted reproduction technology (ART) outcomes and underlying biological mechanisms: protocol of a randomized clinical controlled trial. The "supplementation of vitamin D and reproductive outcome" (SUNDRO) study

Background Vitamin D plays an important role in human physiology and pathology. The receptor for vitamin D regulates 0.5-5% of the human genome. Accordingly, vitamin D insufficiency has been shown to increase the risk of several diseases. In recent years, based on growing evidence, on a role of vitamin D has been also postulated in reproductive health both in animals and humans, especially in female fertility female fertility. In vitro fertilization success was shown to be higher in women with appropriate reserves of vitamin D. However a causal relation has not been demonstrated and randomized controlled trials testing the effectiveness of vitamin D supplementation in IVF are warranted. Methods This is a multicenter randomized double blinded placebo controlled study aimed at determining the benefits of vitamin D [25(OH)D] supplementation in improving clinical pregnancy rate in women undergoing IVF. Eligible women with a serum level of 25-hydroxyvitamin D [25(OH)D] < 30 ng/ml will be randomized. Recruited women will be given the drug (either 600,000 IU of 25(OH) D or placebo in a single oral administration) at the time of randomization. Two centres will participate and the sample size (700 women) is foreseen to be equally distributed between the two. Patients will be treated according to standard IVF protocols. Discussion The primary aim of the study is the cumulative clinical pregnancy rate per oocyte retrieval. Clinical pregnancy is defined as the presence of at least one intrauterine gestational sac with viable foetus at first ultrasound assessment (3 weeks after a positive human chorionic gonadotropin [hCG] assessment). Secondary outcomes include: 1) clinical and embryological variables; 2) oocyte and endometrium quality at a molecular level. To investigate this latter aspect, samples of cumulus cells, follicular and endometrial fluids will be obtained from a subgroup of 50 age-matched good-prognosis cases and controls

Risk of miscarriage in women with endometriosis: insights from in vitro fertilization cycles

Objective: To evaluate whether women with endometriosis achieving singleton pregnancies with IVF face an increased risk of miscarriage. Design: Matched case-control study. Setting: Infertility units. Patient(s): Women achieving singleton pregnancies with the use of IVF were considered. Cases were women with a history of surgery for endometriosis and those who were documented the presence of ovarian endometriomas at the time of the IVF cycle (n = 313). Controls were matched to cases by age (\ub16 months), type of cycle (fresh or frozen cycle). and study period (n = 313). Intervention(s): Retrospective review of women undergoing IVF. Main Outcome Measure(s): Rate of miscarriage before 12 weeks' gestation. Result(s): The number of miscarriages in women with and without endometriosis was similar, being 48 (15%) and 60 (19%), respectively. The odds ratio of miscarriage in affected women was 0.76 (95% confidence interval 0.50-1.16). The odds ratio adjusted for body mass index (BMI), parity, duration of infertility, and male factor infertility was 0.81 (95% confidence interval 0.53-1.25). Subgroup analyses according to the type of cycle, the number of embryos transferred, the presence of endometriomas, and the history of surgery for endometriosis did not document any subgroup at significant increased risk of miscarriage. Conclusion(s): The risk of miscarriage is not increased in women with endometriosis achieving pregnancy with the use of IVF

Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ ICSI cycles

Cycles with progesterone elevation during controlled ovarian stimulation (COS) for IVF/ICSI are commonly managed with a freeze-All strategy, due to a well-recognized detrimental effect of high progesterone levels on endometrial receptivity. However, also a detrimental effect of elevated progesterone on day-3 embryo quality has recently been found with regards to top quality embryo formation rate. Because blastocyst culture and cryopreservation are largely adopted, we deemed relevant to determine whether this detrimental effect is also seen on blastocyst quality on day 5\uc2\ub16. This issue was investigated through a large twocenter retrospective study including 986 GnRH antagonist IVF/ICSI cycles and using top quality blastocyst formation rate as the main outcome. Results showed that on multivariate analysis sperm motility (p1.49 ng/ml as the best cut-off for identification of patients at risk for the absence of top quality blastocysts (AUC 0.55, p<0.01). Our study is the first to investigate the top quality blastocyst formation rate in relation to progesterone levels in IVF/ICSI cycles, showing that increasing progesterone is associated with lower rates of top quality blastocyst. Hence, the advantages of prolonging COS to maximize the number of collected oocytes might eventually be hindered by a decrease in top quality blastocysts available for transfer, if increasing progesterone levels are observed. This observation extends the results of two recent studies focused on day-3 embryos and deserves further research

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 \ub1 3.6 years in women and 39.4 \ub1 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\u2019s age and college degree, smoking habits, calorie and alcohol intake for both partners, previous ART cycles, and partner\u2019s 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\u20131.50) in the second and 0.99 (95% CI 0.71\u20131.40) 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

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. [...]

Comparison of placebo and bromocriptine in the treatment of patients with normoprolactinemic amenorrhoea

Fourteen women with normoprolactinaemic amenorrhoea were treated with bromocriptine (2 . 5 mg twice daily) for a period ranging from 4 to 17 weeks, while a matched group of 19 amenorrhoeic women were treated with a placebo 8one tablet twice daily) for 4 to 12 weeks. About half of the patients in both groups had at least one episode of vaginal bleeding during treatment. There was no clear difference in the menstrual and ovulatory pattern between placebo and bromocriptine groups