The Association Between Immune-Related Conditions Across the Life-Course and Provoked Vulvodynia.

Vulvodynia, impacts up to 8% of women by age 40, and is hypothesized to manifest through an altered immune-inflammatory response. To test this hypothesis, we identified all women born in Sweden between 1973 and 1996 diagnosed with localized provoked vulvodynia (N76.3) and/or vaginismus (N94.2 or F52.5) between 2001 and 2018. We matched each case to two women from the same birth year with no vulvar pain ICD codes. As a proxy for immune dysfunction, we used Swedish Registry data to capture 1) immunodeficiencies, 2) single organ and multiorgan autoimmune conditions, 3) allergy and atopies, and 4) malignancies involving immune cells across the life course. Women with vulvodynia, vaginismus or both were more likely to experience immune deficiencies (OR 1.8, 95% CI, 1.2-2.8), single organ (OR 1.4, 95% CI, 1.2-1.6) and/or multi-organ (OR 1.6, 95% CI, 1.3-1.9) immune disorders, and allergy/atopy conditions (OR 1.7, 95% CI, 1.6-1.8) compared to controls. We observed greater risk with increasing numbers of unique immune related conditions (1 code: OR = 1.6, 95% CI, 1.5-1.7; 2 codes: OR = 2.4, 95% CI, 2.1-2.9; 3 or more codes: OR = 2.9, 1.6-5.4). These findings suggest that women with vulvodynia may have a more compromised immune system either at birth or at points across the life course than women with no vulvar pain history. PERSPECTIVE: Women with vulvodynia are substantially more likely to experience a spectrum of immune related conditions across the life course. These findings lend support to the hypothesis that chronic inflammation initiates the hyperinnervation that causes the debilitating pain in women with vulvodynia.

Interpregnancy interval and maternal and neonatal morbidity: a nationwide cohort study.

This study aimed to assess the association between interpregnancy interval (IPI)-the time from childbirth to conception of the next pregnancy-and maternal and neonatal morbidity. The World Health Organization (WHO) currently recommends an IPI of at least 24 months after a live birth to reduce adverse birth outcomes. However, assessing the relationship between IPI and perinatal outcome is complicated by confounding factors. We conducted a nationwide population-based cohort study using Swedish registry data, allowing for adjustment of maternal characteristics and health at first birth. The study population consisted of all women with a singleton, live, and vaginal first birth with a second singleton birth within five years during 1997-2017, covering 327,912 women and 655,824 neonates. IPI was grouped into six-month intervals with 24-29 months as the reference. The association between IPI and morbidity was examined using multivariate logistic regression. For women having a vaginal delivery at their first birth, intervals < 24-29 months were associated with decreased maternal morbidity and unaffected neonatal morbidity. Intervals > 24-29 months were associated with increased maternal and neonatal morbidity. Our findings question the relevance of WHO's recommendation of an IPI of at least 24 months in a high-income country.

Botulinum Toxin A for Provoked Vestibulodynia: 12 Months' Follow-up of a Randomized Controlled Trial.

BACKGROUND: Provoked vestibulodynia (PVD) is a common pain disorder afflicting primarily young women, and botulinum toxin A (BTA) has been to a limited extent tested as a treatment. AIM: Evaluate outcome 12 months after injection with BTA as a treatment for PVD. METHODS: We conducted a double-blinded, placebo-controlled trial of twice repeated injections of 50 units of BTA or placebo in the bulbocavernosus muscles, 3 months apart, in women with PVD. Treatment outcome after six months', failed to show any significant difference in pain reduction between the groups, as previously reported. Here, we report treatment outcomes 12 months after the first injections. In addition to injections, participants where instructed to perform pelvic floor exercises during month 6-12. 38 participants/group was calculated to achieve a statistical power of 80% based on an effect size of 20 VAS units (mean score range 56-76±31 SD). OUTCOMES: Primary outcome was self-reported dyspareunia or pain at tampon use, using a visual analogue scale (VAS) 0-100. Secondary outcomes were vaginal pressure measurements, psychological health, sexual function and distress. RESULTS: From the initial 88 randomized women with PVD, 75 remained at 12 months; 38 in the BTA and 37 in the placebo group. There was no significant difference in primary outcome between the groups. Vaginal pressure in the BTA group had been restored to pre-treatment levels, with no differences between the groups at 12 months. There was an increase in sexual function in the BTA group, with a Female Sexual Function Index of 22.8 (±4.8) compared to the placebo group to 19.7 (±5.0), P=.048. No differences were observed in sexual distress, stress and anxiety. There was an increase in number of women attempting intercourse in the BTA group (74%) compared with placebo (43%), P=.005. Too few patients performed the pelvic floor exercises for this intervention to be analyzed. CLINICAL IMPLICATIONS: This study highlights BTA as a safe treatment option for patients with PVD. STRENGTHS AND LIMITATIONS: The randomized, double-blinded design and repeated treatments are the major strengths of this study and it is the first study to objectively evaluate muscular effect after BTA injections. The major shortcoming is that few participants performed the pelvic floor exercises, preventing analyses. CONCLUSION: At 12 months' follow up, no significant difference in reduction of dyspareunia or pain at tampon use was observed. Women receiving BTA attempted intercourse more often and improved their sexual function compared with women receiving placebo. Haraldson P, Mühlrad H, Heddini U, et al. Botulinum Toxin A for Provoked Vestibulodynia: 12 Months' Follow-up of a Randomized Controlled Trial. J Sex Med 2022;19:1670-1679.

Delivery mode and severe maternal and neonatal morbidity among singleton term breech births: A population-based cohort study.

OBJECTIVE: The aim of this study was to examine the association between delivery mode and severe maternal and neonatal morbidity in singleton term breech births. STUDY DESIGN: This nationwide population-based cohort study includes 41 319 singleton term and post-term breech births (37 + 0-42 + 6 gestational weeks) in Sweden from 1998 to 2016. Data was retrieved from the Swedish Medical Birth Register. The primary outcomes were two separate composite outcomes, maternal and neonatal severe morbidity. Secondary outcomes were separate severe maternal and neonatal morbidity outcomes. Hospitalization and out-patient visits during childhood were also analyzed in ages 0-5 years. Logistic regression was used to estimate unadjusted and adjusted odds ratios (aOR) with 95% confidence intervals (CI) of severe maternal and neonatal morbidity in women with vaginal breech birth or intrapartum cesarean section. Women with a prelabor breech cesarean section was used as the reference group. RESULTS: No difference between vaginal delivery and prelabor cesarean section was seen regarding maternal morbidity. Intrapartum cesarean section was associated with elevated odds for maternal morbidity (aOR 1.27, 95% CI 1.10-1.47) compared with prelabor cesarean section. A similar result was observed for vaginal delivery and intrapartum cesarean section combined (aOR 1.29, 95% CI 1.11-1.50). Vaginal delivery was associated with higher odds for composite neonatal morbidity (aOR 1.85, CI 1.54-2.21) and most separate outcomes, as well as increased number of hospital nights and out-patient visits during first year of life, compared with prelabor cesarean section. CONCLUSIONS: Prelabor cesarean section in breech births improved short-term neonatal health without increasing risks for severe maternal short-term complications.

Early Life Health in Women with Provoked Vestibulodynia and/or Vaginismus.

Background: The lifetime prevalence of prolonged vulvar pain ranges from 3% to 28% among premenopausal women. Provoked vestibulodynia (PVD), often accompanied with various degrees of vaginismus, is the predominant cause. We explored the association between birth-related events and the risk of developing PVD/vaginismus during adulthood. Materials and Methods: We identified all women born in Sweden between 1973 and 2001 and categorized those with and without a diagnosis of PVD/vaginismus between 2001 and 2016 (during ages 15-43 years). Nationwide registry data were used to estimate the association between health during infancy (preterm birth, low birth weight, small for gestational age [SGA], Appearance, Pulse, Grimace, Activity and Respiration [APGAR] scores <7, and pain exposure during infancy) and the onset of PVD/vaginismus later in life using an event probability model. Results: Of the 1,359,315 women born in Sweden during 1973-2001, 9,247 were diagnosed with PVD (n = 6,648), vaginismus (n = 3,567), or both (n = 969). Preterm delivery <37 weeks (adjusted odds ratios [aOR]: 1.15, 95% confidence interval [CI]: 1.05-1.26), low birth weight <2,500 g (aOR: 1.24, 95% CI: 1.12-1.36), extremely low birth weight <1,500 g (aOR 1.41, 95% CI: 1.10-1.82), and SGA (aOR 1.20, 95% CI: 1.08-1.34) were factors associated with developing PVD/vaginismus. APGAR scores <7 or pain exposure during birth or infancy was not associated with PVD/vaginismus. Advanced maternal age, higher educational attainment, and being born in Sweden were associated with having a female offspring diagnosed with PVD/vaginismus. Conclusions: In a population of Swedish women 15-43 years of age, adverse health at birth was associated with developing PVD/vaginismus later on in life.

Abortion laws and women's health.

We examine the impact of progressive and regressive abortion legislation on women's health in Mexico. Following a 2007 reform in the Federal District of Mexico which decriminalised and subsidised early-term elective abortion, multiple other Mexican states increased sanctions on illegal abortion. We observe that the original legalisation resulted in a sharp decline in maternal morbidity, particularly morbidity due to haemorrhage early in pregnancy. We observe small or null impacts on women's health from increasing sanctions on illegal abortion. These results quantify the considerable improvements in non-mortal health outcomes flowing from legal access to abortion.

Botulinum Toxin A as a Treatment for Provoked Vestibulodynia: A Randomized Controlled Trial.

OBJECTIVE: To evaluate pain reduction after two injections of 50 units botulinum toxin A compared with placebo for provoked vestibulodynia. METHODS: We conducted a double-blinded, placebo-controlled randomized trial of 50 units botulinum toxin A or placebo injected in the bulbocavernosus muscles twice, 3 months apart, in women with provoked vestibulodynia. Primary outcome was self-reported dyspareunia or pain at tampon use on a visual analog scale (VAS, 0-100). Secondary outcomes were pain at weekly tampon insertion (VAS score), reduction of pelvic floor hypertonicity (measured with a vaginal manometer), adverse events, and sexual function and distress. A sample size of 38 participants for each group was calculated to achieve a statistical power of 80% based on an effect size of 20 VAS units (0-100) (mean score range 56-76±31 SD). RESULTS: Between May 2016 and June 2018, 124 women with provoked vestibulodynia were assessed, and 88 were randomized to botulinum toxin A (BTA group, n=44) or placebo (placebo group, n=44). Primary outcome showed a lower but statistically nonsignificant pain rating by 7 VAS units (95% CI -15.0 to 0.4) in the BTA group compared with the placebo group. Secondary results showed a significant decrease in pain at weekly tampon insertion by 11 VAS units (95% CI -16.6 to 6.0) with botulinum toxin A injection. The vaginal manometer measured lower maximum contraction strength by 7 mm Hg (95% CI -12.7 to -2.4) and lower 10-second endurance strength by 4 mm Hg (95% CI -7.72 to -1.16) in the BTA group compared with the placebo group. No changes were observed for sexual function and distress, but there was a significant increase in women attempting vaginal intercourse in the BTA group (0.27, 95% CI 0.06-0.48). No severe adverse events were reported. CONCLUSION: Twice-repeated injections of 50 units of botulinum toxin A in women with provoked vestibulodynia did not reduce dyspareunia or pain at tampon use, but secondary outcomes suggested positive effects of the treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02773641.