Ibuprofen delays ovulation by several hours: prospective controlled study in natural cycles with HCG-triggered ovulation.

RESEARCH QUESTION: Does ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? DESIGN: Two-stage, proof-of-concept, controlled study, assessing the percentage of non-ovulated follicles 42 h after HCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment taking ibuprofen 3 × 400 mg per day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. RESULTS: A total of 26 women were recruited in the ibuprofen intervention group. Twenty-five patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26 [84.6%]; 95% CI 65.1% to 95.6%) was significantly higher than the reference of 50% (P < 0.001). In the control group, the proportion of patients with delayed ovulation was 20.0% ([5/25], 95% CI 6.8% to 40.7%). Compared with the ibuprofen group, a significantly increased probability of a delayed ovulation was found in the ibuprofen intervention group (adjusted OR 22.72, 95% CI 5.77 to 115; P < 0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (90.9%) and all oocytes were mature (metaphase II). CONCLUSIONS: Women trying to conceive should avoid non-selective NSAIDs around the time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in assisted reproductive technology and other infertility treatments if required.

Oocyte maturity, oocyte fertilization and cleavage-stage embryo morphology are better in natural compared with high-dose gonadotrophin stimulated IVF cycles.

RESEARCH QUESTION: Does high-dose gonadotrophin stimulation have an effect on oocyte and early-stage embryo development? DESIGN: This was a retrospective study including 616 natural cycle IVF (NC-IVF) and 167 conventional IVF (cIVF) cycles. In total, 2110 oocytes were retrieved and analysed in fresh cycles. In NC-IVF, only human chorionic gonadotrophin was applied to trigger ovulation. In cIVF, antagonist protocols with daily 150-300 IU of human menopausal gonadotrophins were performed. The effect of gonadotrophins on oocyte and early-stage embryo development was analysed. Primary outcomes were the occurrence of mature (metaphase II) oocytes, zygotes and embryos with good morphology at the cleavage stage 2 days after oocyte retrieval. RESULTS: The mature oocyte rate (number of mature oocytes/number of retrieved oocytes) was higher in NC-IVF than cIVF cycles (89% versus 82%, adjusted odds ratio [aOR] 1.79, P = 0.001), as was the zygote rate per oocyte retrieved (70% versus 58%, aOR 1.76, P = 0.001) and the zygote rate per mature oocyte (79% versus 71%, aOR 1.62, P = 0.001). The percentage of zygotes that developed into cleavage-stage embryos was no different. For the transferred embryos, the probability of having a good embryo morphology with four blastomeres and a fragmentation of <10% (score 0) in cleavage-stage embryos was found to be higher in NC-IVF (proportional aOR for four blastomeres 2.00, P < 0.001; aOR 1.87 for a fragmentation score of 0, P = 0.003). CONCLUSIONS: Oocyte maturity, oocyte fertilization and morphology of the cleavage-stage embryo are affected by high-dose gonadotrophin stimulation in fresh IVF cycles.

Hormone replacement cycles are associated with a higher risk of hypertensive disorders: Retrospective cohort study in singleton and twin pregnancies.

OBJECTIVE: To elaborate the associations of different cycle regimens (natural cycle [NC], stimulated cycle [SC], hormone replacement cycle [HRC]) on maternal and neonatal adverse pregnancy outcomes after frozen-thawed embryo transfers (FET). DESIGN: Population-based registry study. SETTING: Swiss IVF Registry. POPULATION OR SAMPLE: Singleton (n = 4636) and twin (n = 544) live births after NC-FET (n = 776), SC-FET (n = 758) or HRC-FET (n = 3646) registered from 2014 to 2019. METHODS: Fifteen pregnancy pathologies were modelled for singleton and twin pregnancies using mixed models adjusted for cycle regimen, delivery, fertilisation technique, chronic anovulation, age of mother and centre. MAIN OUTCOME MEASURES: Maternal (vaginal bleeding, isolated arterial hypertension and pre-eclampsia) and neonatal (gestational age, birthweight, mode of delivery) adverse pregnancy outcomes. RESULTS: In singleton pregnancies, the incidences of bleeding in first trimester, isolated hypertension and pre-eclampsia were highest in HRC-FET with doubled odds of bleeding in first trimester (adjusted odds ratio [aOR] 2.23; 95% CI 1.33-3.75), isolated hypertension (aOR 2.50; 95% CI 1.02-6.12) and pre-eclampsia (aOR 2.16; 95% CI 1.13-4.12) in HRC-FET vs. NC-FET and with doubled respectively sixfold odds of bleeding (aOR 2.08; 95% CI 1.03-4.21) and pre-eclampsia (6.02; 95% CI 1.38-26.24) in HRC-FET versus SC-FET. In twin pregnancies, the incidence of pre-eclampsia was highest in HRC-FET with numerically higher odds of pre-eclampsia in HRC-FET versus NC-FET and versus SC-FET. CONCLUSIONS: Our data implied the highest maternal risks of hypertensive disorders in HRC-FET, therefore clinicians should prefer SC-FET or NC-FET if medically possible.

Low-dose clomiphene citrate does not reduce implantation and live birth rates in otherwise unstimulated modified natural cycle IVF-retrospective cohort study.

RESEARCH QUESTION: Does antioestrogen effect of clomiphene citrate (CC) on the endometrium reduce implantation and thereby decrease pregnancy and live birth rate per transferred embryo? METHODS: In this cohort, unstimulated IVF cycles modified with clomiphene citrate (CC-NC-IVF) and unstimulated, natural IVF cycles (NC-IVF) conducted between 2011 and 2016 were included. CC was applied in a dosage of 25mcg per day, starting on cycle day 7 until ovulation trigger day. Primary outcomes were clinical pregnancy rate, defined as amniotic sac visible in ultrasound, and live birth rate per transferred embryo. Miscarriage rate calculated as amniotic sac not ending in a live birth was secondary outcome. A modified mixed-effect Poisson regression model was applied, and adjustments were made for female age, parity, type and cause of infertility. Additionally, stratification by parity and age was performed. RESULTS: Four hundred and ninety-nine couples underwent a total of 1042 IVF cycles, 453 being NC-IVF and 589 being CC-NC-IVF cycles. Baseline characteristics of both groups did not differ. Addition of CC did neither decrease clinical pregnancy rate (aRR 0.86; 95% CI 0.67-1.12) nor live birth rate per transferred embryo (aRR 0.84; 95% CI 0.62-1.13) in comparison with NC-IVF. Miscarriage rate did not differ between CC-NC-IVF and NC-IVF (aRR 0.95; 95% CI 0.57-1.57). CONCLUSION: Low-dose CC does not reduce pregnancy or live birth rate per transferred embryo. It can be used in infertility treatment without negatively affecting the endometrium and implantation.

Gonadotrophin stimulation reduces follicular fluid hormone concentrations and disrupts their quantitative association with cumulus cell mRNA.

RESEARCH QUESTION: Do follicular fluid hormone concentrations and the mRNA expression of LHCG, FSH and androgen receptors, aromatase and anti-Müllerian hormone (AMH) in cumulus granulosa cells differ in naturally matured and stimulated follicles? DESIGN: Cross-sectional study involving 57 natural cycle IVF (NC-IVF) and 36 conventional gonadotrophin-stimulated IVF (cIVF) cycles performed between 2014 and 2016. cIVF was performed by ovarian stimulation with human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonists. Hormone concentrations were determined in the follicular fluid of the leading follicle, and mRNA concentrations were quantified by reverse transcription polymerase chain reaction in RNA extracted from granulosa cells of the cumulus oophorus complex obtained from these fluids. RESULTS: Follicular fluid hormone concentrations were significantly lower in cIVF compared with NC-IVF follicles. Median concentrations were 0.50 and 14.5 mIU/ml for LH (P < 0.001), 16.1 and 46.5 nmol/l for testosterone (P < 0.001), 1270 and 2675 nmol/l for oestradiol (P < 0.001), and 12.3 and 28.9 pmol/l for AMH (P < 0.001), respectively. In cumulus granulosa cells, mRNA concentrations for LH receptor, FSH receptor, androgen receptor, aromatase and AMH did not differ between cIVF and NC-IVF follicles. Several hormone and mRNA concentrations were quantitatively associated in natural cycles such as follicular fluid AMH and cumulus granulosa cells AMH RNA (r2 = 0.107, P = 0.013), follicular fluid testosterone and cumulus granulosa cell AMH RNA (r2 = 0.158, P = 0.002), follicular fluid oestradiol and cumulus granulosa cell AMH RNA (r2 = 0.105, P = 0.014) and follicular fluid oestradiol and aromatase (r2 = 0.113, P = 0.011). In contrast, these associations were not observed in stimulated cycles. CONCLUSION: These findings indicate some effects of gonadotrophin stimulation on follicular physiology, which could be a cause for the previously suggested lower oocyte quality in cIVF compared with NC-IVF.

Perinatal outcomes in singletons after fresh IVF/ICSI: results of two cohorts and the birth registry.

RESEARCH QUESTION: How are perinatal outcomes of live-born singletons after stimulated and unstimulated IVF different from perinatal outcomes in (i) children born in a tertiary centre and (ii) all children born in Switzerland? METHODS: This cohort study compared the perinatal outcomes of two birth cohorts and the national live birth registry. Relative risks were calculated using modified Poisson regression and clustering for siblings and adjustment for maternal age, parity and childs sex. RESULTS: Of the 636,639 live births, 311 were in the Bern IVF Cohort (144 stimulated, 167 unstimulated), 2332 in the tertiary centre and 633,996 in the Swiss Live Birth Registry (SLBR). Perinatal outcomes following IVF did not differ compared with births in the SLBR (adjusted relative risk [aRR]; 95% confidence interval [CI]), with the exception of the increased risk of small for gestational age (1.31; 1.01 to 1.70, P = 0.04; aRR 1.12; 0.87 to 1.45, P = 0.39). Children born following stimulated IVF had a higher risk of low birthweight (2.17; 1.27 to 3.69, P < 0.01; aRR 1.72; 1.01 to 2.93, P = 0.05), and of being small for gestational age (1.50; 1.05 to 2.14, P = 0.03; aRR 1.31; 0.92 to 1.87; P = 0.13), whereas children born after unstimulated IVF had no increased risks compared with the SLBR. Higher Caesarean rate after IVF was mainly associated with higher maternal age. CONCLUSION: Singletons in the Bern IVF Cohort do not show less favourable perinatal outcomes. Gonadotrophin stimulation seems to have an effect, because lower risks were associated with unstimulated IVF.

The case for mild stimulation for IVF: recommendations from The International Society for Mild Approaches in Assisted Reproduction.

The practice of ovarian stimulation for IVF is undergoing a fundamental re-evaluation as recent data begin to successfully challenge the traditional paradigm that ovarian stimulation should be aimed at the retrieval of as many oocytes as possible, in the belief that this will increase pregnancy rates. An opposing view is that live birth rate should not be the only end-point in evaluating the success of IVF treatment and that equal emphasis should be placed on safety and affordability. The International Society for Mild Approaches in Assisted Reproduction (ISMAAR) committee has carried out an up-to-date literature search, with the evidence being graded according to the University of Oxford's Centre for Evidence-Based Medicine. The recommendations were formulated taking into account the quality of evidence on the efficacy, risk and cost of each intervention. ISMAAR recommends adopting a mild approach to ovarian stimulation in all clinical settings as an increasing body of evidence suggests that mild stimulation is as effective as conventional stimulation, while being safer and less expensive. Mild ovarian stimulation could replace conventional stimulation, thus making IVF safer and more accessible worldwide.

Awareness of non-communicable diseases in women: a cross-sectional study.

Chronic non-communicable diseases (NCD) are the major reason for death, morbidity, loss of independency and public health cost. NCD prevalence could be significantly reduced by adopting a healthy lifestyle. This cross-sectional cohort study (online survey) in 221 women aimed to assess NCD awareness, knowledge about NCD prevention and willingness to adopt a healthier lifestyle in women. Overall, NCD awareness level was quite high with, however, information mainly originating from lay media, probably being one reason for false estimations of age groups mainly affected by NCD, impact of NCD on quality of life, NCD mortalities, and the extent of NCD prevention by lifestyle interventions, respectively. Furthermore, also due to mainly lay media, half of women knew online NCD risk calculators, most of them would like to know their NCD risk, but only few had been offered NCD risk calculation by their physician. The mean threshold for willing to adopt a healthier lifestyle was a roughly calculated 37% 5-10 years risk to develop a certain NCD. Acceptance of non-pharmacological interventions for NCD prevention was high, however, major barriers for not implementing a healthier lifestyle were lack of expert information and lack of time. In conclusion, future public health strategies should focus on distributing better understandable and correct information about NCD as well as meeting the individuals' request for personalized NCD risk calculation. Furthermore, physicians should be better trained for personalized NCD prevention counseling.

Impact of chronic stress exposure on cognitive performance incorporating the active and healthy aging (AHA) concept within the cross-sectional Bern Cohort Study 2014 (BeCS-14).

PURPOSE: This study aims to verify that the mental-cognitive domain of the validated generic bio-functional status (BFS)/bio-functional age (BFA) assessment tool, incorporating the concept of Active and Healthy Ageing (AHA), reflects cognitive performance. In addition, the effects of chronic stress exposure on the mental-cognitive BFS/BFA should be investigated. METHODS: The study was carried out as a monocenter, cross-sectional, observational, non-interventional trial (Bern Cohort Study 2014, BeCS-14) with the participation of 147 non-pediatric, non-geriatric subjects. All participants followed a standardized battery of biopsychosocial assessments consisting of BFS/BFA, a validated cognitive performance test battery (Inventar zur Gedächtnisdiagnostik; IGD) and a validated questionnaire for the assessment of chronic stress (Trier Inventory for the assessment of Chronic Stress; TICS), respectively. RESULTS: Mean cognitive performance was average and higher in younger or better educated individuals. The BFA of the participants was 7.8 ± 7.8 year-equivalents below their chronological age. The mental-cognitive BFS/BFA assessment correlated well with the validated questionnaire for cognition assessment, the IGD. Further, three TICS subdomains (work overload (r = - 0.246, p = 0.003), work discontent (r = - 0.299, p = 0.006) and pressure to succeed (r = - 0.274, p < 0.001)), reflecting mainly work-related stress, showed a significant negative correlation with the mental-cognitive BFS/BFA. CONCLUSIONS: Our study shows that the BFS/BFA assessment tool follows European Innovation Partnership on Active and Healthy Ageing (EIP-AHA) requirements. Further, we could demonstrate that higher levels of chronic work-related stress may be associated with poorer mental-cognitive performance and a pro-aging state indicating that cognitive impairments can be reduced by stress management interventions.

The endocrine milieu in naturally matured follicles is different in women with high serum anti-Müllerian hormone concentrations.

RESEARCH QUESTION: Is the endocrine milieu different in women with low serum anti-Müllerian hormone (AMH) concentration compared with women with high concentration? DESIGN: Cohort study of 84 women (four groups) classified according to AMH concentration and age undergoing natural cycle IVF treatment. Concentrations of LH, oestradiol, testosterone, androstenedione and AMH were determined in follicular fluid (FF), associations analysed and clinical outcome parameters evaluated. RESULTS: A positive correlation between serum and FF AMH concentrations was confirmed. Follicular fluid androstenedione concentration was positively correlated with serum AMH concentration (P < 0.0001, r2 = 0.197). The correlation between FF LH and FF testosterone concentration in all women was not significant (P = 0.050, r2 = 0.046); however, the correlation between FF androstenedione in women with high serum AMH concentration was significant (P = 0.032, r2 = 0.220). Follicular fluid testosterone and androstenedione were positively correlated with FF oestradiol overall and in some individual groups. The high serum AMH concentration group showed the highest FF AMH and androstenedione concentrations and lowest oestradiol-testosterone and oestradiol-androstenedione ratios. High FF AMH concentration was associated with a higher clinical pregnancy rate and high FF oestradiol concentration with a slightly better embryo quality. CONCLUSIONS: Differences in the endocrine milieu in women with high serum AMH concentration seem to be caused by increased follicular LH concentration. In women with high serum AMH concentration, FF androstenedione is increased and ratios of oestradiol-testosterone and oestradiol-androstenedione are decreased, suggesting a disturbed endocrine milieu caused by reduced metabolization of FF androgens into oestrogens. In natural cycles, FF AMH concentrations are positively associated with higher clinical pregnancy rates and oestradiol concentrations with a higher embryo score.

Breastfeeding following in vitro fertilisation in Switzerland-Does mode of conception affect breastfeeding behaviour?

AIM: Breastfeeding has numerous advantages. Our aim was to investigate whether breastfeeding initiation and duration in women with pregnancies conceived through in vitro fertilisation differ from spontaneously conceived pregnancies. METHODS: This is a comparative cross-sectional study about breastfeeding behaviour performed at the Bern University Hospital including mothers of singletons conceived by in vitro fertilisation (n = 198) with or without gonadotropin stimulation between 2010 and 2016 (in vitro fertilisation group). They were compared to a population-based control group (n = 1421) of a randomly selected sample of mothers in Switzerland who delivered in 2014. RESULTS: A total of 1619 women were included in this analysis. Breastfeeding initiation rates were high, similar between the in vitro fertilisation group (93.4%) and the control group (94.8%). No increased risk of stopping breastfeeding earlier after in vitro fertilisation treatment compared to the control group could be found over the observational period of 12 months (HR = 1.00, 95% CI 0.83-1.20, P = .984). There was no difference in breastfeeding initiation or duration after gonadotropin-stimulated vs unstimulated in vitro fertilisation. CONCLUSION: In Switzerland, in vitro fertilisation treatments were not associated with earlier breastfeeding cessation. This result is reassuring for mothers undergoing in vitro fertilisation.

Regulation and adaptation of endocrine axes at high altitude.

As a model of extreme conditions, eight healthy women, part of a 40-member Nepal mountain-climbing expedition, were monitored for dynamic endocrine adaptations. Endocrine measurements were made at frequent intervals over a 6-10-h period at four altitudes: 450 m, 4,800 m (base camp), 6,050 m, and again at 4,800 m (on descent) after an acclimatization (A) period (4,800 mA). Quantified hormones were growth hormone (GH), prolactin (PROL), cortisol (Cort), thyroid-stimulating hormone (TSH), and free thyroxine. These hormones are important to the anabolic/catabolic balance of the body, and are vital to growth, homeostasis, hypothalamic inhibition, regulation of stress, and metabolism. A key secondary question was the degree to which acclimatization can stabilize hormonal disruption. On the basis of statistical false discovery rates, the present analyses unveil marked adaptive changes in the thyroid axis at the level of pulsatile secretion of the pituitary hormone TSH and its downstream product, free thyroxine; strong effects on the mass of GH, TSH, Cort, and PROL secretion per burst; and prominent pulsatile frequency disruption and recovery for PROL and Cort. Because pulsatility changes reflect de facto perturbations in hypothalamo-pituitary control mechanisms, the present data introduce the concept of both frequency- and amplitude-dependent adaptive control of brain-pituitary neuroendocrine signals under conditions of extreme altitude exertion and exposure.

The indication for fertility preservation in women with Turner syndrome should not only be based on the ovarian reserve but also on the genotype and expected future health status.

Fertility preservation in women with Turner syndrome is highly controversial. Some strongly recommend freezing of ovarian tissue at a young age, others do not. The controversy is partly due to different perspectives and professions. Biologists prefer to freeze young ovaries with high follicle density, reproductive physicians want to avoid risky operations and iatrogenic infertility by removing one ovary, and cardiologists and obstetricians warn against the risks of later pregnancies. Accordingly, fertility preservation in young women with Turner syndrome is more than just the freezing of ovarian tissue or oocytes. Fertility preservation requires a balanced decision considering the conservation of fertility, the protection of reproductive health, and future health consequences. Therefore, fertility preservation strategies should be based not only on the individual ovarian reserve but also on the genotype and the expected cardiac health status to decide what is the best option: to freeze tissue or alternatively to wait and see.

Overnight ovarian tissue transportation for centralized cryobanking: a feasible option.

RESEARCH QUESTION: Is overnight transportation of ovarian tissue before cryopreservation in a centralized cryobank from the FertiPROTEKT network feasible? DESIGN: Data from 1810 women with cryopreserved ovarian tissue after overnight transportation from December 2000 to December 2017 were analysed with a focus on transportation, tissue activity parameters and pregnancy, and delivery rates after transplantation. RESULTS: A total of 92.4% of tissue samples arrived at ideal temperatures of 2-8°C, 0.4% were transported at temperatures lower than ideal and 6.4% were transported at temperatures that were too high, generally due to mishandling of the inlayed cool packs of the transportation boxes. In 62 women, 78 tissue transplantations were carried out. A subgroup of 30 women who underwent a single orthotopic transplantation with fulfilled criteria of a complete follow-up after transplantation until the end of study, a premature ovarian insufficiency after gonadotoxic therapy as well as the absence of pelvic radiation, was further analysed. In this group, transplantations into a peritoneal pocket accounted for 90%. Transplants were still active at 1 year and above after transplantation in 93.3%. Pregnancy and delivery rates were 46.7% and 43.3%, respectively, with one ongoing pregnancy at the end of the study. CONCLUSIONS: Overnight transportation for central cryobanking is a feasible concept that results in high reproducible success rates through standardized professional tissue freezing and storage.

The greater incidence of small-for-gestational-age newborns after gonadotropin-stimulated in vitro fertilization with a supraphysiological estradiol level on ovulation trigger day.

INTRODUCTION: Reproductive scientists have postulated various risk factors for lower birthweight following conventional gonadotropin-stimulated in vitro fertilization compared with spontaneously conceived children: parental factors (age, health, duration of subfertility and smoking habits); ovarian stimulation; laboratory procedures; the number of oocytes retrieved and the number of embryos transferred. Our aim was to investigate the impact of gonadotropin stimulation and serum estradiol level on the risk of a newborn being small-for-gestational-age. MATERIAL AND METHODS: We conducted a cohort study (2010-2016) of singletons (n = 155) born either after conventional gonadotropin-stimulated in vitro fertilization (using ≥150 IU/d human gonadotropin for stimulation) or after natural cycle in vitro fertilization without any stimulation. We analyzed perinatal outcomes using birthweight percentiles, adjusted for gestational age and sex. RESULTS: The proportion of small-for-gestational-age was 11.8% following conventional gonadotropin-stimulated in vitro fertilization and 2.9% after natural cycle in vitro fertilization (P = 0.058). The odds of small-for-gestational-age were significantly higher with supraphysiological estradiol levels in maternal serum on ovulation trigger day (unadjusted odds ratio 4.58; 95% confidence interval 1.35-15.55; P = 0.015). It remained significant after adjusting for maternal height, age and body mass index (adjusted odds ratio 3.83; 95% confidence interval 1.06-13.82; P = 0.041). CONCLUSIONS: We found an associated risk of children being born small-for-gestational-age after conventional gonadotropin-stimulated in vitro fertilization compared with natural cycle in vitro fertilization. This higher risk is significantly associated with supraphysiological estradiol levels. We propose a reduction in the dosage of gonadotropin to minimize the risk of small-for-gestational-age and future health consequences.

Only women's age and the duration of infertility are the prognostic factors for the success rate of natural cycle IVF.

PURPOSE: It is controversial who should be recommended to undergo natural cycle IVF (NC-IVF). Therefore, objective prognostic criteria which are already known at the time of counselling were defined. METHODS: A retrospective observational study was performed with 201 couples (age 34.7 ± 4.1) undergoing 311 NC-IVF treatments with 201 transfers, corresponding to a transfer rate of 65.3%. The first cycle resulting in a transfer of one embryo was further analysed. Clinical pregnancy and live birth rates were analysed. RESULTS: Pregnancy rate and live birth rates per first cycle were 21.9% and 13.2%, respectively. Groupwise comparison revealed the following clinical pregnancy/live birth rates per transfer cycle: duration of infertility 1-2 years 34.3/25.7%, 3-4 years 21.8/14.9% and > 4 years 9.1/4.5%. Women's age < 34 years 26.3/22.4%, 34-37 years 25.7/18.9% and 38-42 years 15.7/3.9%. Linear regression analysis showed that pregnancy and live birth rate correlated negatively with the duration of infertility and that live birth rate but not pregnancy rate correlated negatively with increasing female age. In contrast, AMH and infertility factors did not correlate with the success rate. Statistically significant correlations remained if a multivariate logistic regression analysis was performed, supporting further that the duration of infertility (OR 0.61, 95% CI 0.42-0.86) (P = 0.006) and female age (OR 0.87, 95% CI 0.78-0.95) (P = 0.008) are the predictors for live birth rates in NC-IVF transfer cycles. CONCLUSIONS: Based on the success rates, NC-IVF can especially be recommended for women with short duration of infertility and young age, whereas older women and those with long duration of infertility are not the best candidates for this technique.

Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue.

Fertility-preserving measures are becoming important for patients receiving oncological treatment. One method involves cryopreservation of ovarian tissue and transplanting it when treatment is completed. We report complications resulting from surgical and fertility medicine, and the results of procedures for the removal and transplantation of ovarian tissue carried out within the FertiProtekt network. A survey using a structured questionnaire was conducted among the FertiProtekt network centres between November 2015 and June 2016. The analysis included surgical techniques used to remove and transplant ovarian tissue, surgical complications and results. Laparoscopic removal and transplantation of ovarian tissue have a low risk of complications. Surgical complications occurred in three of the network's 1373 ovarian tissue removals (n = 1302) and transplantations (n = 71); two complications (0.2%) occurred during removal and one during transplantation. Menstruation resumed in 47 out of 58 women (81%) who underwent ovarian tissue transplantation. Hormonal activity occurred in 63.2% of transplantations with a follow-up of 6 months or over. Sixteen pregnancies occurred in 14 patients, with nine births. The risks and complications of removal and transplantation of ovarian tissue are similar to those of standard laparoscopy. These procedures are becoming standard for fertility protection in cancer patients.

Treatment-related psychological stress in different in vitro fertilization therapies with and without gonadotropin stimulation.

INTRODUCTION: Infertility treatments such as in vitro fertilization (IVF) impose substantial distress. However, the specific role of individual contributory factors remains unclear. We therefore compared treatment-related psychological stress in IVF treatments with (cIVF) and without (NC-IVF) gonadotropin stimulation, as cIVF includes potentially stressful factors such as ovarian stimulation, anesthesia, embryo selection and cryopreservation, whereas NC-IVF does not. MATERIAL AND METHODS: Women were offered to have cIVF or NC-IVF. Validated psychological questionnaires filled in online before, during and after completed treatment cycle(s) at home were used to analyze psychological distress and treatment-related satisfaction and quality of life. To avoid different pregnancy rates in the two treatment groups, one cIVF was compared with three NC-IVF therapies, resulting in the same cumulative pregnancy rate. RESULTS: Data from 57 NC-IVF and 62 cIVF patients were evaluated. NC-IVF resulted in a similar overall clinical pregnancy rate than one cIVF. NC-IVF patients had a significantly lower level of depression (CES-D, 13.4 vs. 15.7, p < 0.05) and a higher satisfaction with the treatment (Treatment FertiQoL, 67.9 vs. 62.9, p < 0.05) compared with cIVF patients. The level of psychological distress increased during c-IVF treatment and decreased during NC-IVF treatment. In contrast, during NC-IVF treatment there was a significant increase in satisfaction with the treatment, whereas satisfaction with treatment in the cIVF patients decreased. CONCLUSIONS: Factors other than just pregnancy rate seem to have an impact on psychological stress in IVF treatment. Due to reduced psychological stress in NC-IVF, this treatment could be especially considered in psychologically stressed women.

[Fertility Preservation in Prepubertal und Pubertal Children and Adolescents]. / Fertilitätserhalt bei präpubertären und pubertären Kindern und Jugendlichen.

BACKGROUND: Due to rising survival rates in cancer and autoimmune diseases fertility preservation before gonadotoxic therapies has become increasingly important. Although fertility can be significantly affected by gonadotoxic therapies, the possibility of fertility preservation during childhood has not been sufficiently considered so far. METHODS: Selective literature research with presentation of fertility preservation methods, their indications, implementations, risks and efficacy. RESULTS: Measures are indicated in all girls and boys at high risk of gonadal damage. The complexity of the techniques requires special expertise in the counseling and implementation, which is offered to girls in counselling Germany especially in the centers of FertiPROTEKT (www.fertiprotekt.com). In girls, mainly cryopreservation of ovary tissue is considered. In postpubertal girls cryopreservation of oocytes is also possible. In postpubertal boys sperm can be preserved. Freezing of testicular tissue is still experimental in prepubertal boys. Success rates are still difficult to quantify; birth rates of about 50% are discussed. All procedures are not covered by health insurance. CONCLUSION: In children and adolescents, measures of fertility preservation should be considered in cases of highly gonadotoxic therapies, and appropriate advice should be given by specialists.

Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part II: fertility preservation techniques.

PURPOSE: In addition to guidelines focusing on scientific evidence, practical recommendations on fertility preservation are also needed. METHODS: A selective literature search was performed based on the clinical and scientific experience of the authors. This article (Part II) focuses on fertility preservation techniques. Part I, also published in this journal, provides information on disease prognosis, disease-specific therapy, and risks for loss of fertility. RESULTS: Ovarian stimulation including double stimulation and freezing of oocytes is the best-established therapy providing live birth chances in women < 35 years with high ovarian reserve of around 30-40%. Ovarian tissue freezing is especially useful in young women with good ovarian, if spontaneous conception is favoured and if < 1 week until chemotherapy is provided. Data on success rates are still limited, but this further evolving technique will possibly reach similar success rates as ovarian stimulation. GnRH agonists seem to reduce the risk of premature ovarian failure up to 50%; however, the effect is possibly not long-lasting. Ovarian transposition can easily be combined with freezing of ovarian tissue and is the preferred technique before pelvic radiotherapy. Other techniques, such as in vitro maturation, are limited to women with high ovarian reserve and remain less effective. In addition, procedures such as in vitro growth of follicles, etc. are still experimental. CONCLUSIONS: Fertility preservation in women provides realistic chances of becoming pregnant. The choice of technique needs to be based on the time required, the woman's age, its risks and efficacy, and the individual preference of the patient.