Fertility Preservation in Female Patients with Cancer

Advances in cancer treatment with resultant dramatic improvements in long-term survival have led to increasing awareness of the wide range of medical and social issues faced by survivors of malignancy. The potential deleterious effects on fertility are a significant worry of women and trans gender men, and the rising trend in delaying childbearing and the higher proportion of patients who have not completed their family at the time of diagnosis increases the demand for an optimised fertility-preservation service. Fertility preservation for this group following a diagnosis of cancer is a rapidly expanding area of reproductive medicine, although provision for such treatment often varies by region. In the past, there were few treatment options, but with dramatic improvements in oocyte cryopreservation and, more recently, ovarian tissue cryopreservation, this area of fertility care has broadened substantially. This review will be exploring areas that apply to all cisgender women, but not necessarily all trans men and non-binary individuals. There are specific considerations in fertility preservation for trans people, which are beyond the scope of this paper. All individuals with female reproductive organs should be offered the opportunity to discuss fertility preservation prior to starting potential gonadotoxic treatment. Failure to do this may negatively influence their anticancer treatment choices and adherence to treatment regimens. There are currently few networks streamlined around offering this service and as demand for these treatment options increases, it is recognised that these complex patients require specialist management within recognised care pathways. Here we are looking to describe some of the unique challenges associated with providing a state-of-the-art service, particularly in a financially unpredictable climate in the midst of the COVID-19 pandemic.     

输卵管疾病的生育力保护

输卵管因素不孕症占不孕人群的30%～35%。随着腹腔镜技术及微创手术原则的应用，生殖相关输卵管性疾病的微创手术治疗受到关注。手术治疗输卵管性不孕在评估输卵管功能，保留生育功能，改善患者自然妊娠或辅助生殖技术助孕的结局方面具有重要作用。文章主要对有生育要求的输卵管病变患者，腹腔镜手术保留及恢复生育功能的处理及临床结局进行阐述。     

Reproduction patterns among classical Hodgkin lymphoma survivors treated with BEACOPP and ABVD in Sweden,Denmark and Norway—A population-based matched cohort study

Childbirth rates in classical Hodgkin lymphoma (cHL) survivors have historically been reduced compared to the general population. Understanding if contemporary treatment protocols are associated with reduced fertility is crucial as treatment guidelines shift toward more liberal use of intensive chemotherapy. We identified 2834 individuals aged 18-40 years with cHL in Swedish and Danish lymphoma registers, and in the clinical database at Oslo University Hospital diagnosed 1995-2018, who were linked to national medical birth registers. Cox regression adjusted for stage, performance status, year, and age at diagnosis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) contrasting time to first childbirth by treatment groups (ABVD, 2-4 BEACOPP, 6-8 BEACOPP) up to 10 years after diagnosis. Overall, 74.8% of patients were treated with ABVD, 3.1% with 2-4 BEACOPP and 11.2% with 6-8 BEACOPP. Adjusted HRs comparing childbirth rates in individuals treated with 6-8 BEACOPP, and 2-4 BEACOPP to ABVD were 0.53 (CI: 0.36-0.77) and 0.33 (CI: 0.12-0.91) for males, and 0.91 (CI: 0.61-1.34) and 0.38 (CI: 0.12-1.21) for females. Cumulative incidence of childbirths after 10 years was 19.8% (CI: 14.5%-27.0%) for males and 34.3% (CI: 25.8%-45.6%) for females treated with 6-8 BEACOPP. Proportions of children born after assisted reproductive technique (ART) treatments were 77.4% (CI: 60.2-88.6%) for males following 6-8 BEACOPP, and <11% for females. Among ABVD treated patients the corresponding proportions were 12.2% (CI: 8.5%-17.3%) and 10.6% (CI: 7.4%-14.9%). BEACOPP treatment is associated with decreased childbirth rates compared to ABVD in male, but not female, cHL patients, despite widespread access to ART in the Nordics.     

《傅青主女科》“种子”辨治特色探析

《傅青主女科》为中国清代医家傅山所著,具有鲜明的学术特色,受后世医家推崇,为中医妇科学的继承和发展作出巨大贡献。该书中《种子篇》论治不孕尤具特色,擅抓主症,辨证详明,理法严谨,用药精简。其种子理念重视脏腑辨证,以补肾益精为主,在此基础上注重健脾疏肝养血,交通心肾,灵活应用阴阳、五行学说及经络理论协调各脏腑关系,进而促进孕育,对临证治疗不孕症具有一定的指导意义。     

Relationship between early‐life nutrition and ages at menarche and first pregnancy,and childbirth rates of young adults: Evidence from APCAPS in India

India's Integrated Child Development Services (ICDS) provides daily supplementary nutrition and other public health services to women and children. We estimated associations between exposure to early‐childhood ICDS nutrition and adult reproductive outcomes. During 1987–1990, a balanced protein–calorie supplement called “upma”—made from locally available corn–soya ingredients—was rolled out by subdistricts near Hyderabad and offered to pregnant women and children under age 6 years. In a controlled trial, 15 villages received the supplement and 14 did not. We used data from a 2010–2012 resurvey of adults born during the trial (n = 715 in intervention and n = 645 in control arms). We used propensity score matching methods to estimate the associations between birth in an intervention village and menarcheal age, age at first pregnancy, and fertility of adults. We found that women born in the intervention group during the trial, as compared with the control group, had menarche 0.45 (95% confidence interval [CI: 0.22, 0.68]; p < .001) years later and first pregnancy 0.53 (95% CI [0.04, 1.02]; p < .05) years later. Married women from the intervention group had menarche 0.36 (95% CI [0.09, 0.64]; p < .01) years later, first cohabitation with partner 0.8 (95% CI [0.27, 1.33]; p < .01) years later, and first pregnancy 0.53 (95% CI [0.04, 1.02]; p < .05) years later than married women in the control group. There was no significant difference between intervention and control group women regarding whether they had at least one childbirth or the total number of children born. The findings were similar when we employed inverse propensity score weighted regression models.     

Perfect- and typical-use effectiveness of the Dot fertility app over 13 cycles: results from a prospective contraceptive effectiveness trial

Objective: Dynamic Optimal Timing (Dot) is a smartphone application (app) that estimates the menstrual cycle fertile window based on the user’s menstrual period start dates. Dot uses machine learning to adapt to cycles over time and informs users of ‘low’ and ‘high’ fertility days. We investigated Dot’s effectiveness, calculating perfect- and typical-use failure rates.

Methods: This prospective, 13 cycle observational study (ClinicalTrials.gov NCT02833922) followed 718 women who were using Dot to prevent pregnancy. Participants contributed 6616 cycles between February 2017 and October 2018, providing data on menstrual period start dates, daily sexual activity and prospective intent to prevent pregnancy. We determined pregnancy through participant-administered urine pregnancy tests and/or written or verbal confirmation. We calculated perfect- and typical-use failure rates using multi-censoring, single-decrement life-table analysis, and conducted sensitivity, attrition and survival analyses.

Results: The perfect-use failure rate was calculated to be 1.0% (95% confidence interval [CI]: 0.9%, 2.9%) and the typical-use failure rate was 5.0% (95% CI: 3.4%, 6.6%) for women aged 18–39 (n?=?718). Survival analyses identified no significant differences among age or racial/ethnic groups or women in different types of relationships. Attrition analyses revealed no significant sociodemographic differences, except in age, between women completing 13 cycles and those exiting the study earlier.

Conclusion: Dot’s effectiveness is within the range of other user-initiated contraceptive methods.     

The effect of cancer on reproductive health

The incidence of cancer and survival rates are increasing, as is the consequent impact on reproductive health. Delay in childbearing years is also an important factor. It is well documented that a significant number of cancer treatments are gonadotoxic. This can lead to fertility concerns and long term effects for both men and women. Fertility preservation should only take place if the patient is well enough, where there is time and if it will not worsen their oncological condition. In men, fertility preservation is a straightforward procedure, whereas in women it is more invasive, carries more risk and can significantly delay cancer treatment. The long term effects of cancer treatment include early menopause, erectile dysfunction, loss of libido and psychosexual dysfunction. These factors can significantly affect quality of life. Hence, well organised referral pathways and counselling services are paramount and must include a multidisciplinary approach involving relevant specialists.     

The toxicology of gallium oxide in comparison with gallium arsenide and indium oxide

Gallium arsenide (GaAs) and indium oxide (In₂O₃) are used in electronic industries at high and increasing tonnages since decades. Gallium oxide (Ga₂O₃) is an emerging wide-bandgap transparent conductive oxide with as yet little industrial use. Since GaAs has received critical attention due to the arsenic ion, it seemed reasonable to compare its toxicology with the respective endpoints of Ga₂O₃ and In₂O₃ toxicology in order to find out if and to what extent arsenic contributes. In addition, the toxicology of Ga₂O₃ has not yet been adequately reviewed, Therefore, this review provides the first evaluation of all available toxicity data on Ga₂O₃. The acute toxicity of all three compounds is rather low. Subchronic inhalation studies in rats and mice revealed persistent pulmonary alveolar proteinosis (PAP) and/or alveolar histiocytic infiltrates down to the lowest tested concentration in rats and mice, i.e. 0.16 mg Ga₂O₃/m³. These are also the predominant effects after GaAs and In₂O₃ exposure at similarly low levels, i.e. 0.1 mg/m³ each.Subchronic Ga₂O₃ exposure caused a minimal microcytic anemia with erythrocytosis in rats (at 6.4 mg/m³ and greater) and mice (at 32 and 64 mg/m³), a decrease in epididymal sperm motility and concentration as well as testicular degeneration at 64 mg/m³. At comparable concentrations the hematological effects and male fertility of GaAs were much stronger.The stronger effects of GaAs are due to its better solubility and presumed higher bioavailability. The database for In₂O₃ is too small and subchronic testing was at very low levels to allow conclusive judgements if blood/blood forming or degrading and male fertility organs/tissues would also be targets.