Delayed childbearing and female ageing impair assisted reproductive technology outcome in survivors of male haematological cancers.

PURPOSE: To analyse the impact of female characteristics on assisted reproductive technology outcome among male haematological cancer survivors. METHODS: A retrospective analysis of 93 haematological cancer survivors attending our tertiary referral fertility centre between June 1998 and June 2017 for achieving fatherhood with assisted reproductive technology treatments. RESULTS: A progressive increase in the median female age was observed during the study period (32.2 years until the year 2007 and 36.9 years from the year 2012). Fifty-five out of 93 patients were treated with intracytoplasmic sperm injection (ICSI) (113 ovarian stimulations, 108 ICSI procedures). Cryopreserved ejaculated sperm was used in 28 couples, fresh sperm in 19, and thawed testicular sperm in 8 couples. Mean female age at ovarian stimulation was 37.0 ± 4.7 years. Twenty-six pregnancies resulted in a full-term birth (23% per started ovarian stimulation; 43.6% per couple) and 33 children were born. No significant differences were observed according to source of sperm (fresh, frozen, testicular) and multivariate analysis confirmed that maternal age was the only variable inversely related to the cumulative delivery rate, being five times lower (15.7%) when the female partner was ≥ 40 years (OR = 0.22, 95% CI 0.06-0.77) vs. 58.3% with younger women (p = 0.0037). CONCLUSIONS: Delayed childbearing and female ageing affect ICSI outcome in couples where the male is a survivor of haematological cancer. This topic should be discussed when counselling male cancer patients about fertility preservation.

Levothyroxine supplementation on assisted reproduction technology (ART) outcomes in women with subtle hypothyroidism: a retrospective study.

The need for treating subclinical hypothyroidism (SCH) in women undergoing assisted reproduction technology (ART) is under debate. Moreover, it is known that controlled ovarian hyperstimulation (COH) protocols may impair the thyroidal axis. Therefore, we evaluated if levothyroxine (L-T4) supplementation in SCH women before undergoing ART positively affects the main reproductive outcomes. We retrospectively analyzed in vitro fertilization (IVF) data of 4147 women submitted to 6545 cycles in a tertiary care IVF Center (January 2009-December 2014). L-T4 (1.4-2.0 mcg/kg) treatment was offered to all women with a pre-cycle TSH >2.5 mIU/L before starting COH and main ART outcomes were compared in euthyroid and L-T4-treated women undergoing ART. Among 4147 women, 1074 (26%) were affected by SCH and were treated with L-T4 before COH was started. No statistically significant differences among L-T4-treated and euthyroid women group were observed regarding pregnancy rate, respectively, per cycle (27.67% vs 26.37%; p = .314) and per embryo transfer (30.13% vs 29.17%; p = .489), live birth rate, respectively, per cycle (21.58% vs 20.38%; p = .304) and per embryo transfer (23.49 vs 22.54%; p = .449) and the rest of primary and secondary efficacy endpoints. Early L-T4 treatment for infertile women with a subtle thyroid dysfunction may mitigate and protect from the negative effects of SCH in the setting of ART, and may preventively overcome also the negative impact of COH on thyroidal axis.

The effect of parnaparin sodium on in vitro fertilization outcome: A prospective randomized controlled trial.

INTRODUCTION: In-vitro and in-vivo models suggest the influence of low-molecular weight heparin on conception in infertile women undergoing in vitro fertilization procedures (IVF). In this randomized controlled trial we assessed whether a low-molecular weight heparin (parnaparin) could affect IVF outcomes. MATERIALS AND METHODS: 271cycles were analyzed in 247 women having a first or subsequent IVF cycle at Fertility Center of Humanitas Research Hospital. Patients, without severe thrombophilia and hormonal or active untreated autoimmune disorders, were randomly allocated (1:1) to receive for the whole cycle parnaparin, or routine hormonal therapy only. The primary endpoint was the clinical pregnancy rate and the secondary endpoints included implantation rate and live birth rate. RESULTS: The clinical pregnancy and the live birth rate were similar in treated and controls (21.5% vs. 26.7%, p=0.389; 18.5% vs. 20.6%, p=0.757). The abortion rate was 10.3% vs 22.9%, p=0.319, respectively. The subgroups analysis, ≤35, 36-38, 39-40years, showed the following: comparable clinical pregnancy rate (22.5% vs 38.8%, p=0.124; 21.8% vs 17.3%, p=0.631; 19.4% vs 23.3%, p=0.762 respectively) and live birth rate (16.3% vs 32.7%, p=0.099; 20.0% vs 13.5%, p=0.443; 19.4% vs 13.3%, p=0.731 respectively) in treated vs controls. Sensitivity analyses on women with ≥3 previous attempts and first enrolment only, and subgroup analyses according to trial conclusion conditioning a small sample size with low statistical power. CONCLUSIONS: Our study excludes positive effect of parnaparin, once a day for the whole cycle, on clinical pregnancy rate in infertile women undergoing in vitro fertilization techniques.