Long-term male fertility after treatment with radioactive iodine for differentiated thyroid carcinoma.

CONTEXT: Whilst radioactive iodine (RAI) is often administered in the treatment for differentiated thyroid carcinoma (DTC), long-term data on male fertility after RAI are scarce. OBJECTIVE: To evaluate long-term male fertility after RAI for DTC, and to compare semen quality before and after RAI. DESIGN, SETTING, AND PATIENTS: Multicenter study including males with DTC ≥2 years after their final RAI treatment with a cumulative activity of ≥3.7 GBq. MAIN OUTCOME MEASURE(S): Semen analysis, hormonal evaluation, and a fertility-focused questionnaire. Cut-off scores for 'low semen quality' were based on reference values of the general population as defined by the World Health Organization (WHO). RESULTS: Fifty-one participants had a median age of 40.5 (interquartile range (IQR): 34.0-49.6) years upon evaluation and a median follow-up of 5.8 (IQR: 3.0-9.5) years after their last RAI administration. The median cumulative administered activity of RAI was 7.4 (range: 3.7-23.3) GBq. The proportion of males with a low semen volume, concentration, progressive motility, or total motile sperm count did not differ from the 10th percentile cut-off of a general population (P = 0.500, P = 0.131, P = 0.094, and P = 0.500, respectively). Cryopreserved semen was used by 1 participant of the 20 who had preserved semen. CONCLUSIONS: Participants had a normal long-term semen quality. The proportion of participants with low semen quality parameters scoring below the 10th percentile did not differ from the general population. Cryopreservation of semen of males with DTC is not crucial for conceiving a child after RAI administration but may be considered in individual cases.

Male subfertility and oxidative stress.

To date 15% of couples are suffering from infertility with 45-50% of males being responsible. With an increase in paternal age as well as various environmental and lifestyle factors worsening these figures are expected to increase. As the so-called free radical theory of infertility suggests, free radicals or reactive oxygen species (ROS) play an essential role in this process. However, ROS also fulfill important functions for instance in sperm maturation. The aim of this review article is to discuss the role reactive oxygen species play in male fertility and how these are influenced by lifestyle, age or disease. We will further discuss how these ROS are measured and how they can be avoided during in-vitro fertilization.

Long-Term Effects of Radioiodine Treatment on Female Fertility in Survivors of Childhood Differentiated Thyroid Carcinoma.

Background: Differentiated thyroid carcinoma (DTC) during childhood is a rare disease. Its excellent survival rate requires a focus on possible long-term adverse effects. This study aimed to evaluate fertility in female survivors of childhood DTC by assessing various reproductive characteristics combined with anti-Müllerian hormone (AMH) levels (a marker of ovarian reserve). Methods: Female survivors of childhood DTC, diagnosed at ≤18 years of age between 1970 and 2013, were included. Survivors were excluded when follow-up time was less than five years or if they developed other malignancies before or after diagnosis of DTC. Survivors filled out a questionnaire regarding reproductive characteristics (e.g., age at menarche and menopause, pregnancies, pregnancy outcomes, need for assisted reproductive therapy). Survivors aged <18 years during evaluation received an altered questionnaire without questions regarding pregnancy and pregnancy outcomes. These data were combined with information from medical records. AMH levels were measured in serum samples and were compared with AMH levels from 420 women not treated for cancer. Results: Fifty-six survivors with a median age of 31.0 (interquartile range, IQR, 25.1-39.6) years were evaluated after a median follow-up of 15.4 (IQR 8.3-24.7) years. The median cumulative dose of 131I administered was 7.4 (IQR 3.7-13.0) GBq/200.0 (IQR 100.0-350.0) mCi. Twenty-five of the 55 survivors aged 18 years or older during evaluation reported 64 pregnancies, 45 of which resulted in live birth. Of these 55, 10.9% visited a fertility clinic. None of the survivors reported premature menopause. Age at AMH evaluation did not differ between DTC survivors and the comparison group (p = 0.268). Median AMH levels did not differ between DTC survivors and the comparison group [2.0 (IQR 1.0-3.7) µg/L vs. 1.6 (IQR 0.6-3.1) µg/L, respectively, p = 0.244]. The cumulative dose of 131I was not associated with AMH levels in DTC survivors (rs = 0.210, p = 0.130). Conclusions: Female survivors of DTC who received 131I treatment during childhood do not appear to have major abnormalities in reproductive characteristics nor in predictors of ovarian failure.

Reduced oxygen concentration during human IVF culture improves embryo utilization and cumulative pregnancy rates per cycle.

STUDY QUESTION: Do different oxygen levels during human IVF embryo culture affect embryo utilization, cumulative IVF success rates per cycle and neonatal birthweight? SUMMARY ANSWER: After 2 days of culture, a lower oxygen level (5%) leads to more good-quality embryos and more embryos that can be cryopreserved, and thereby to a higher cumulative live birth rate per cycle when compared to embryo culture in 20% oxygen, while birthweights are similar. WHAT IS KNOWN ALREADY: Several studies have compared IVF outcome parameters after embryo culture in a more physiological level of 5% oxygen and the atmospheric level of 20%. Although there is consensus that embryo development improves in 5% oxygen, effects on pregnancy and live birth rates are mainly seen in blastocyst, but not cleavage-stage transfers. A major drawback of these studies is that only fresh embryo transfers were included, not taking additional frozen-thawed transfers from these cycles into account. This might have underestimated the effects of oxygen level, especially in cleavage-stage embryo transfers. Furthermore, little is known about the effect of oxygen level during culture on birthweight. STUDY DESIGN SIZE DURATION: This is a cohort study in 871 consecutive patients who had an IVF cycle between January 2012 and December 2013, and 5-7 years follow-up to allow transfer of frozen-thawed embryos. Based on daily availability of positions in the incubators, all oocytes and embryos of one cycle were allocated to one of the three incubators with traditional ambient oxygen levels (6% CO2 and 20% O2 in air), or to a fourth incubator that was adjusted to have low oxygen levels of 5% (6% CO2, 5% O2 and 89% N2). Embryos were cultured under 5 or 20% oxygen until Day 2 or 3, when embryos were transferred or cryopreserved, respectively. Clinical and other laboratory procedures were similar in both groups. PARTICIPANTS/MATERIALS SETTING METHODS: To compare embryo characteristics and (cumulative) pregnancy outcomes between the two oxygen groups, for each patient only the first cycle in the study period was included in the analysis, resulting in 195 cycles in the 5% group (1627 oocytes) and 676 in the 20% oxygen group (5448 oocytes). Embryo characteristics were analysed per cycle and per embryo and were corrected for maternal age, cycle rank order, fertilization method (IVF or ICSI) and cause of subfertility. Perinatal data from the resulting singletons (n = 124 after fresh and 45 after frozen-thawed embryo transfer) were collected from delivery reports from the hospitals or midwife practices. MAIN RESULTS AND THE ROLE OF CHANCE: In the 5% oxygen group, there were significantly more embryos of good quality (45.8 versus 30.9% in the 20% group, adjusted odds ratio (OR) [95% CI] = 1.9 [1.6-2.4]). This did not result in higher live birth rates per cycle, but after fresh transfers more good-quality spare embryos could be cryopreserved (46.1 versus 29.7%, adjusted OR [95% CI] = 2.0 [1.7-2.5]).After a follow-up period of 5-7 years, in which 82.4% of the cryopreserved embryos from the 5% oxygen group and 85.4% from the 20% oxygen group were thawed, the percentage of patients with at least one live birth resulting from the study cycle was significantly higher in the low oxygen group (adjusted OR [95% CI] = 1.5 [1.01-2.2]). In 124 live born singletons from fresh embryo transfers and in 45 from transfers of cryopreserved embryos, birthweight was similar in both oxygen groups after correction for confounding factors. LIMITATIONS REASONS FOR CAUTION: This is a retrospective study, and treatment allocation was not randomised. The study was not powered for a predefined birthweight difference. With the number of live births in our study, small differences in birthweight might not have been detected. The selection of embryos to be cryopreserved was based on embryo morphology criteria that might be different in other clinics. WIDER IMPLICATIONS OF THE FINDINGS: Improved embryo utilization by more cryopreservation leading to higher cumulative live birth rates per cycle favours the use of 5% instead of 20% oxygen during human IVF embryo culture. This study also demonstrates that for comparison of different IVF treatment regimens, the cumulative outcome, including transfers of fresh and frozen-thawed embryos, is to be preferred instead of analysis of fresh embryo transfers only. STUDY FUNDING/COMPETING INTERESTS: No external funding was received for this study. None of the authors has a conflict of interest to declare. TRIAL REGISTRATION NUMBER: NA.

[IVF in a modified natural cycle]. / Ivf in de gemodificeerde natuurlijke cyclus.

In vitro fertilisation (IVF) usually involves controlled ovarian stimulation (COS). There is now increasing emphasis on methods that make IVF safer and more patient-friendly. Modified natural cycle (MNC)-IVF is an example of this. In MNC-IVF spontaneous ovulation is prevented with a minimal amount of hormones and spontaneous monofollicular growth is supported. As a result, there is no risk of ovarian hyperstimulation syndrome, and the risk of a multiple pregnancy is low. There is a 9.1% chance of a pregnancy after one MNC-cycle and the cumulative pregnancy rate after a maximum of 6 MNC-IVF cycles is 33.4%. The cumulative results of a maximum of 6 MNC-IVF cycles are comparable to those of the first COS-IVF treatment cycle including transfer of cryopreserved embryos produced as a result of the treatment (33.4% versus 37.7%). The risk of a twin pregnancy following MNC-IVF is 0.1%, and 18.3% following COS-IVF. This means that MNC-IVF is a good alternative for COS-IVF.

Embryo quality and impact of specific embryo characteristics on ongoing implantation in unselected embryos derived from modified natural cycle in vitro fertilization.

OBJECTIVE: To study the implantation potential of unselected embryos derived from modified natural cycle IVF according to their morphological characteristics. DESIGN: Cohort study. SETTING: Academic department of reproductive medicine. PATIENT(S): A series of 449 single embryo transfers derived from modified natural cycle IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ongoing implantation rate according to embryo characteristics. RESULT(S): The best implantation was found in embryos with 4 and 8 cells on day 2 and 3 respectively,

In vitro fertilization with preimplantation genetic screening.

BACKGROUND: Pregnancy rates in women of advanced maternal age undergoing in vitro fertilization (IVF) are disappointingly low. It has been suggested that the use of preimplantation genetic screening of cleavage-stage embryos for aneuploidies may improve the effectiveness of IVF in these women. METHODS: We conducted a multicenter, randomized, double-blind, controlled trial comparing three cycles of IVF with and without preimplantation genetic screening in women 35 through 41 years of age. The primary outcome measure was ongoing pregnancy at 12 weeks of gestation. The secondary outcome measures were biochemical pregnancy, clinical pregnancy, miscarriage, and live birth. RESULTS: Four hundred eight women (206 assigned to preimplantation genetic screening and 202 assigned to the control group) underwent 836 cycles of IVF (434 cycles with and 402 cycles without preimplantation genetic screening). The ongoing-pregnancy rate was significantly lower in the women assigned to preimplantation genetic screening (52 of 206 women [25%]) than in those not assigned to preimplantation genetic screening (74 of 202 women [37%]; rate ratio, 0.69; 95% confidence interval [CI], 0.51 to 0.93). The women assigned to preimplantation genetic screening also had a significantly lower live-birth rate (49 of 206 women [24%] vs. 71 of 202 women [35%]; rate ratio, 0.68; 95% CI, 0.50 to 0.92). CONCLUSIONS: Preimplantation genetic screening did not increase but instead significantly reduced the rates of ongoing pregnancies and live births after IVF in women of advanced maternal age. (Current Controlled Trials number, ISRCTN76355836 [controlled-trials.com].).