Fertility counselling and fertility preservation among early onset female cancer patients-A Finnish register-based study.

INTRODUCTION: Advances in multimodality cancer treatments have increased long-term survival rates for early onset cancer patients, with 5-year survival rates reaching 80% in Northern Europe. According to recent recommendations, clinicians should, as early as possible, inform cancer patients about the impact that cancer treatment may have on their fertility. Still, there is limited published data on fertility counselling (FC) and fertility preservation (FP) for cancer patients. METHODS: This register-based study used hospital records to identify female cancer patients in the hospital district (n = 192) who received FC at the age of 16-42 years between 2011 and 2019. RESULTS: Altogether, 97 (50.5%) cancer patients were eligible for FP. Of these, 55 (56.7%) underwent FP, whereas 42 (43.3%) declined. Women undergoing FP were recommended cancer treatments with a higher risk of infertility (p = 0.01), and women with breast cancer were more prone to undergo FP than women with lymphoma (p = 0.043). In FP treatment cycles, the mean number of oocytes retrieved (13.9 ± 7.7 vs. 12.0 ± 6.5, p = 0.04) and transferrable embryos (4.7 ± 2.9 vs. 3.7 ± 2.8, p = 0.002) was higher among cancer patients compared to age-matched comparisons with male or tubal factor infertility. The total mean gonadotropin dose used was higher among cancer patients (2243 ± 963 IU vs. 1679 ± 765 IU, p < 0.001). CONCLUSION: We conclude that a good ovarian response during FP can be achieved in female cancer patients.

Quantification of urinary total luteinizing hormone immunoreactivity may improve the prediction of ovulation time.

Objectives: Most of the currently available ovulation prediction kits provide a relatively rough estimation of ovulation time with a short fertility window. This is due to their focus on the maximum probability of conception occurring one day before ovulation, with no follow-up after LH surge until ovulation nor during the subsequent days thereafter. Earlier studies have shown that urine of reproductive age women contains at least 3 different molecular forms of luteinizing hormone (LH); 1) intact LH, 2) LH beta-subunit (LHß) and a 3) small molecular weight fragment of LHß, LHß core fragment (LHßcf). The proportion of these LH forms in urine varies remarkably during the menstrual cycle, particularly in relation to the mid-cycle LH surge. In this exploratory study, we studied the potential implications of determining the periovulatory course of total LH immunoreactivity in urine (U-LH-ir) and intact LH immunoreactivity in serum (S-LH-ir) in the evaluation of the fertility window from a broader aspect with emphasis on the post-surge segment. Methods: We determined total U-LH-ir in addition to intact S-LH-ir, follicle-stimulating hormone (FSH), progesterone, and estradiol in 32 consecutive samples collected daily from 10 women at reproductive age. Inference to the non-intact U-LH-ir levels was made by calculating the proportion of total U-LH-ir to intact S-LH-ir. Results: Total U-LH-ir increased along with LH surge and remained at statistically significantly higher levels than those in serum for 5 consecutive days after the surge in S-LH-ir. S-LH-ir returned to follicular phase levels immediately on the following day after the LH surge, whereas the same took 7 days for total U-LH-ir. Conclusions: The current exploratory study provides preliminary evidence of the fact that U-LH-ir derived from degradation products of LH remains detectable at peak levels from the LH surge until ovulation and further during the early postovulatory period of fecundability. Thus, non-intact (or total) U-LH-ir appears to be a promising marker in the evaluation of the post-surge segment of the fertility window. Future studies are needed to unravel if this method can improve the prediction of ovulation time and higher rates of fecundability in both natural and assisted conception.

Somatic Health and Psychosocial Background Among Finnish Adolescents with Gender Dysphoria Seeking Hormonal Interventions.

Purpose: Although the number of young adults suffering from gender dysphoria (GD) is increasing, reports focusing on their somatic health remain scarce. We studied the somatic health, pubertal development, psychosocial background, and interest regarding gender-affirming surgical treatment of Finnish adolescents seeking gender-affirming hormonal treatment (GAHT). Methods: In this retrospective register study at an adolescent gynecology clinic in Helsinki University Hospital, Finland we included 124 adolescents diagnosed with GD and referred to GAHT between January 1, 2011 and December 31, 2018. This cohort covered two thirds of all Finnish adolescents referred to GAHT during the follow-up. Data on the general adolescent population were obtained from the Finnish School Health Promotion (SHP) study of year 2017. Results: Most adolescents were assigned female at birth. Sex ratio increased from 1.2 in 2012 to 5.2 in 2017. One-third of the patients were overweight or obese (body mass index [BMI] >25 kg/m2). Other somatic comorbidities were rare. Interest toward reconstructive genital surgery was more common among male-to-female than female-to-male patients (80% vs. 22%, respectively, p<0.001). Depression (29%) and anxiety (19%) were common psychiatric comorbidities. Parental divorce rate (57%) was higher than in the general adolescent population in Finland (23%, p<0.001). Conclusion: Finnish adolescents diagnosed with GD-seeking GAHT have good somatic health, but a higher proportion of overweight, depression, and anxiety than the general adolescent population. Prospective follow-up of this cohort will provide an opportunity to evaluate the somatic and psychosocial outcomes and quality of life during GAHT.

Endocrine Disorders and Genital Infections Impair Gynecological Health in APECED (APS-1).

Objective: In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) defects in the autoimmune regulator gene lead to impaired immunotolerance. We explored the effects of immunodeficiency and endocrinopathies on gynecologic health in patients with APECED. Design: Cross-sectional cohort study combined with longitudinal follow-up data. Methods: We carried out a gynecologic evaluation, pelvic ultrasound, and laboratory and microbiologic assessment in 19 women with APECED. Retrospective data were collected from previous study visits and hospital records. Results: The study subjects' median age was 42.6 years (range, 16.7-65.5). Sixteen patients (84%) had premature ovarian insufficiency, diagnosed at the median age of 16.5 years; 75% of them used currently either combined contraception or hormonal replacement therapy. In 76% of women, the morphology and size of the uterus were determined normal for age, menopausal status, and current hormonal therapy. Fifteen patients (79%) had primary adrenal insufficiency; three of them used dehydroepiandrosterone substitution. All androgen concentrations were under the detection limit in 11 patients (58%). Genital infections were detected in nine patients (47%); most of them were asymptomatic. Gynecologic C. albicans infection was detected in four patients (21%); one of the strains was resistant to azoles. Five patients (26%) had human papillomavirus infection, three of which were high-risk subtypes. Cervical cell atypia was detected in one patient. No correlation between genital infections and anti-cytokine autoantibodies was found. Conclusions: Ovarian and adrenal insufficiencies manifested with very low androgen levels in over half of the patients. Asymptomatic genital infections, but not cervical cell atypia, were common in female patients with APECED.

Norethisterone and its acetate - what's so special about them?

INTRODUCTION: Progestogens (progestins) are widely used for contraception, in postmenopausal hormone therapy, and in treatment of abnormal uterine bleeding and endometriosis. Norethisterone (NET) and its acetate (NETA) differ from other progestogens by their partial conversion to ethinylestradiol (EE). We review their special characteristics and focus on the clinically relevant risk factors associated with estrogen action, such as migraine with aura and risk of thrombosis. METHODS: Narrative review based on a medical literature (OvidMedline and PubMed) search. RESULTS: NET converts to significant amounts of EE; 10-20 mg NET corresponds to 20-30 µg EE. The effects of NET on the endometrium are pronounced, making it a good choice for treating abnormal uterine bleeding, endometriosis, and endometrial hyperplasia. NET also has beneficial effects on bone mineral density and positive or neutral effects on cardiovascular health. Conversely, long-term use of NET is associated with a slightly increased breast cancer risk, and the risk of venous thromboembolism is moderately increased. This risk seems to be dose-dependent; contraceptive use carries no risk, but therapeutic doses might be associated with an increased risk. Studies suggest an association between combinations of EE and progestogens and ischaemic stroke, which in particular concerns women with migraine. No studies have, however, assessed this risk related to the therapeutic use of NET. CONCLUSIONS: NET is a potent progestogen, especially when considering the endometrium. Its partial conversion to EE, however, is important to remember. Clinical consideration is required with women at high risk for either breast cancer or thromboembolism, or experiencing migraine with aura.

Outcomes of 42 pregnancies in 14 women with cartilage-hair hypoplasia: a retrospective cohort study.

BACKGROUND: Cartilage-hair hypoplasia (CHH) is a rare skeletal dysplasia characterized by disproportionate short stature, immunodeficiency, anemia and risk of malignancies. All these features can affect pregnancy and predispose to maternal and fetal complications. This study aimed to evaluate obstetric history and maternal and fetal outcomes in women with CHH. METHODS: Among 47 Finnish women with CHH, we identified 14 women with ICD codes related to pregnancies, childbirth and puerperium in the National Hospital Discharge Registry and obtained detailed data on gynecologic and obstetric history with a questionnaire. Offspring birth length and weight were collected and compared with population-based normal values. RESULTS: There were altogether 42 pregnancies in 14 women (median height 124 cm, range 105-139 cm; 4'1'', range 3'5''-4'7''). Twenty-six pregnancies (62%), including one twin pregnancy, led to a delivery. Miscarriages, induced abortions and ectopic pregnancies complicated 9, 5, and 2 pregnancies, respectively. Severe pregnancy-related complications were rare. All women with CHH delivered by cesarean section, mostly due to evident cephalo-pelvic disproportion, and in 25/26 cases at full-term. In the majority, the birth length (median 48 cm, range 45.5-50 cm; 1'7'', range 1'6''-1'8'') and weight (3010 g, range 2100-3320 g; 6.6 lb, range 4.6-7.3 lb) of the offspring in full-term singleton pregnancies was normal. CONCLUSIONS: Despite CHH mothers' significant short stature and other potential CHH-related effects on pregnancy outcome, most pregnancies lead to a term cesarean section delivery. Since fetal growth was generally unaffected, cephalo-pelvic disproportion was evident and planned cesarean section should be contemplated in term pregnancies.

Gynecologic health in cartilage-hair hypoplasia: A survey of 26 adult females.

Cartilage-hair hypoplasia (CHH) is a rare metaphyseal chondrodysplasia significantly affecting adult height and quality of life. Immunodeficiency and increased risk for malignancies contribute to significant morbidity. Little is known about gynecologic health in CHH. We performed a questionnaire study of 26 women (mean age 42.3 years) with genetically confirmed CHH, inquiring about pubertal development, menstrual cycle, use of contraception, pregnancies, gynecologic infections, and gynecologic cancers. Mean age at menarche and menopause was 12.7 and 46.1 years, respectively. Mean length of menstrual cycle was 27 days. Contraception was used by 76%, most commonly condom (60%), and combined contraception (60%). Despite significant short stature (mean height 121 cm) and potentially small pelvic diameters, 10 CHH women (38%) had been pregnant. Six of these women reported miscarriages and three had, induced pregnancy terminations. Eight women had in total, 19 deliveries. Abnormal Pap smear was reported in five patients and cervical cancer once. Our findings of normal timing of puberty and menopause suggest a fairly normal length of the fertility period in women with CHH. However, many patients expressed concerns regarding the safety of pregnancy and lack of prepregnancy counseling. Immunodeficiency may predispose CHH women to prolonged HPV infections. This study highlights the importance of careful gynecologic follow-up for these patients.

Gynecologic assessment of 19 adult females with cartilage-hair hypoplasia - high rate of HPV positivity.

BACKGROUND: Patients with cartilage-hair hypoplasia (CHH), a rare metaphyseal chondrodysplasia, manifest severe growth failure, variable immunodeficiency and increased risk of malignancies. The impact of CHH on gynecologic and reproductive health is unknown. Vulnerability to genital infections may predispose CHH patients to prolonged human papillomavirus (HPV) infections potentially leading to cervical, vaginal and vulvar cancer. METHODS: We carried out gynecologic evaluation, pelvic ultrasound and laboratory assessment in 19 women with genetically confirmed CHH. All patients were clinically examined and retrospective data were collected from hospital records. RESULTS: The women ranged in age from 19.2 to 70.8 years (median 40.8 years) and in height from 103 to 150 cm (median 123 cm). All women had undergone normal pubertal development as assessed by breast development according to Tanner scale and by age of menarche (mean 12.5 yrs., range 11-14 yrs). Despite significant short stature and potentially small pelvic diameters, a well-developed uterus with fairly normal size and shape was found by pelvic ultrasound in most of the patients. Ovarian follicle reserve, assessed by ultrasound was normal in relation to age in all premenopausal women it could be assessed (12 cases). Anti-Müllerian hormone was normal in relation to age in 17 women (89%). HPV was detected in 44% (8/18) and three women carried more than one HPV serotype; findings did not associate with immunological parameters. Three patients had a concurrent cell atypia in Pap smear. CONCLUSIONS: Pubertal development, reproductive hormones and ovarian structure and function were usually normal in women with CHH suggesting fairly normal reproductive health. However, the immunodeficiency characteristic to CHH may predispose the patients to HPV infections. High prevalence of HPV infections detected in this series highlights the importance of careful gynecologic follow up of these patients.

Diversity of Pubertal Development in Cartilage-Hair Hypoplasia; Two Illustrative Cases.

BACKGROUND: Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia, including disproportionate short stature, hypoplastic hair, immunodeficiency, and increased risk of malignancies. Absent pubertal growth spurt and absent pubic hair complicate monitoring of pubertal development in these patients. CASES: Two CHH patients with delayed puberty and excessive growth failure are described. One of the girls had hypogonadotropic hypogonadism whereas the other had hyponormogonadotropic hypogonadism with no spontaneous pubertal development and slow response to estrogen therapy, both requiring permanent replacement therapy. SUMMARY AND CONCLUSION: Careful follow-up of pubertal development in individuals with CHH and other growth-restricting bone diseases is needed. In delayed pubertal development timely hormone therapy is essential to ensure maximal growth and well developed secondary sex characteristics.

Detecting early kidney damage in horses with colic by measuring matrix metalloproteinase -9 and -2, other enzymes, urinary glucose and total proteins.

BACKGROUND: The aim of the study was to investigate urine matrix metalloproteinase (MMP-2 and -9) activity, alkaline phosphatase/creatinine (U-AP/Cr) and gamma-glutamyl-transpeptidase/creatinine (U-GGT/Cr) ratios, glucose concentration, and urine protein/creatinine (U-Prot/Cr) ratio and to compare data with plasma MMP-2 and -9 activity, cystatin-C and creatinine concentrations in colic horses and healthy controls. Horses with surgical colic (n = 5) were compared to healthy stallions (n = 7) that came for castration. Blood and urine samples were collected. MMP gelatinolytic activity was measured by zymography. RESULTS: We found out that horses with colic had significantly higher urinary MMP-9 complex and proMMP-9 activities than horses in the control group. Colic horses also had higher plasma MMP-2 activity than the control horses. Serum creatinine, although within reference range, was significantly higher in the colic horses than in the control group. There was no significant increase in urinary alkaline phosphatase, gamma-glutamyltranspeptidase or total proteins in the colic horses compared to the control group. A human cystatin-C test (Dako Cytomation latex immunoassay based on turbidimetry) did not cross react with equine cystatin-C. CONCLUSION: The results indicate that plasma MMP-2 may play a role in the pathogenesis of equine colic and urinary MMP-9 in equine kidney damage.

Etiological diagnosis of childhood pneumonia by use of transthoracic needle aspiration and modern microbiological methods.

Childhood pneumonia is usually treated without determining its etiology. The causative organism can be isolated from specimens of blood, empyema fluid, or lung aspirate, but this is rarely done. The potential of transthoracic needle aspiration for identification of causative agents was tested with use of modern microbiological methods. Aspiration was performed for 34 children who had radiological signs compatible with community-acquired pneumonia and had alveolar consolidation. In addition to bacterial and viral cultures and viral antigen detection, nucleic acid detection for common respiratory pathogens was performed on aspirate specimens. Aspiration disclosed the etiology in 20 (59%) of 34 cases overall and in 18 (69%) of 26 patients from whom a representative specimen was obtained. Aspiration's advantages are high microbiological yield and a relatively low risk of a clinically significant adverse event. Aspiration should be used if identification of the causative agent outweighs the modest risk of the procedure.