Fertility and sterility最新文献

Assisted Reproductive Medicine (ART) has become the primary treatment of infertility. As such, ART has been regulated by certain authorities and primarily, structured by various scientific organisms through recommendations and guidelines. Yet, these have limits - the topic addressed here - and may at times need to rely on grit for managing the totally unexpected. Doctors must also cope with what is not addressed by these guidelines, including the couple's desire for final family size.

Objective: To expand knowledge on physical outcomes and psychosocial experiences of oocyte donors after donation across 3 age cohorts.

Design: Cross-sectional mixed-methods survey.

Patients: A total of 363 participants (ages: 22-71 years, M = 38.8) recruited from Donor Sibling Registry and Facebook groups donated an average of 3.3 times, with 77.1% using nonidentified donation. Most were White (92.8%) and over half (59%) were married at the time of survey. Average length of time from initial donation to study participation was 13.75 years.

Exposure: Previous oocyte donation.

Main outcome measures: Self-reported physical outcomes and psychological experiences after donation.

Results: Most donors (89.5%) completing the online survey (N = 363) reported a positive overall experience. Self-reported physical outcomes, including changes to menstrual cycles, ovulation, or fertility, were reported by 21% of participants after donation. Many (41.4%) reported procedural pain, and 10.5% reported ovarian hyperstimulation syndrome. Anxiety (25.8%) and depression (23.2%) were the most common self-reported diagnoses. Validated measures (Patient Reported Outcomes Measurement Information System Bank V1.0 Depression, Patient Reported Outcomes Measurement Information System Bank V1.0 Anxiety) were used to assess mild or greater anxiety and depression (25.1% and 17.6%, respectively; t-score ≥55). Participants screened clinically significant rates of alcohol/drug misuse (11.5%; ≥2 Cut down, Annoyed, Guilty, Eye opener-Adapted to Include Drugs), with 50% of those reporting depressive symptoms. Anonymity was the most common qualitative response for reported emotional distress (17%) and regret (20%). Most participants (94.3%) reported no contact by clinics for medical updates after donation, despite 25% reporting they had changes in their health to communicate. Participants' open-ended responses detailed the 3 most important concerns: improved communication with clinics; desire for less anonymity; and more information on long-term donor health outcomes.

Conclusion: Most participants felt their oocyte donation experience was positive despite reported pain, menstrual cycle changes, and emotional distress. Depression and anxiety were the most common self-reported diagnoses. Depression rated higher than the national prevalence. Elevated Cut down, Annoyed, Guilty, Eye opener-Adapted to Include Drugs was associated with depression, indicating the importance of screening oocyte donors for mental health and drug/alcohol misuse. Concerns included lack of communication after procedure and lack of information provided on long-term health outcomes. Clinicians can incorporate these findings when counseling this population.

Objective: To study ferritin levels, and potential factors influencing them, in women with polycystic ovary syndrome (PCOS), and to investigate potential associations between ferritin levels and other parameters in these women.

Design: Longitudinal general population -based cohort study, including data from both questionnaires and clinical measurements.

Subjects: The study was conducted with data from the participants of the Women's Health Study, including a total of 1918 Finnish women, around 35 years of age.

Exposure: PCOS was defined according to the Rotterdam criteria by the presence of at least two of the following findings: oligo/amenorrhea, hyperandrogenism (clinical or biochemical), and polycystic ovarian morphology.

Main outcome measures: Serum ferritin levels and other parameters were determined from the cohort data and the associations between ferritin levels and other investigated parameters were investigated with linear regression models.

Results: Women with PCOS had significantly higher median ferritin levels than women without PCOS (51.43 μg/L vs 44.85 μg/L, p=0.020). Low ferritin levels were less common among women with PCOS who had oligo- or amenorrhea than in those who did not (1.5% vs 11.8%, p=0.024). Median ferritin levels were also found to be lower in hyperandrogenic women with PCOS than in those with normoandrogenemia (49.96 μg/L vs 73.50 μg/L, p=0.011). Women with PCOS had higher fasting insulin levels than women without PCOS (8.85 mU/L vs 7.60 mU/L), and a positive association between fasting insulin and ferritin levels was found in the whole population (effect size: 0.0619, 95% confidence intervals: 0.005; 0.119, p=0.034). Finally, associations between ferritin levels and history of infertility were investigated in both the total population and in women with PCOS, but no significant associations were found.

Conclusion: Our results suggest that women with PCOS have higher ferritin levels than those without PCOS, and that both the decreased blood loss from irregular menstruation and elevated androgen levels can influence ferritin levels in women with PCOS. A metabolic connection was also found as serum insulin levels associated positively with serum ferritin levels in the total population, whereas history of infertility did not seem to associate with serum ferritin levels in any of the study groups.

Background: Thrombin prefers substrates carrying Arg at the site of cleavage (P1) because of the presence of D189 in the primary specificity (S1) pocket but can also cleave substrates carrying Phe at P1. The structural basis of this property is unknown.

Objective: Solve the X-ray structure of thrombin bound to a ligand carrying Phe at P1 and investigate the effects of replacing D189.

Methods: X-ray crystallography is used to solve the structure of thrombin bound to the irreversible inhibitor H-D-Phe-Pro-Phe-CH₂Cl (PPPCK). Residue D189 is mutated to Ala, Lys, Phe and Ser.

Results: The X-ray structure of the thrombin-PPPCK complex is solved at 2.5 Å resolution and compared to the structure of thrombin bound to H-D-Phe-Pro-Arg-CH₂Cl (PPACK). PPPCK binds to thrombin in a conformation similar to that of PPACK, but Phe at P1 makes no contacts with D189. Replacement of D189 with Ala, Lys, Phe or Ser reverses both substrate preference and stability enhancement from Arg to Phe.

Conclusions: D189 in the S1 pocket confers thrombin "trypsin-like" specificity for Arg at P1. However, the S1 pocket is wide enough to also enable "chymotrypsin-like" specificity for Phe at P1. Consistent with these structural features, a single amino acid replacement (D189A) switches thrombin specificity from trypsin-like to chymotrypsin-like, converting the substrate preference from H-D-Phe-Pro-Arg-p-nitroanilide to H-D-Phe-Pro-Phe-p-nitroanilide and preferential stability enhancement from PPACK to PPPCK. The observation that thrombin specificity is controlled mainly by a single residue establishes a new paradigm in the field of trypsin-like proteases.