Objective: To review the effect of the COVID-19 pandemic on the presentation of Cervical cancer. Design/ Setting: Retrospective study involving the Regional Cancer Centres in the M62 Group. Methods: Data was collected for two equal time periods. All cervical cancers were included and FIGO 2018 staging was used for the data collection. P values were calculated using binomial hypothesis test for the difference in staging. Time from symptoms to diagnosis was assessed using a normal distribution test. All other calculations were performed using chi-squared test. Statistical significance was considered if p values were <0.05. Main outcome measures: Histology, stage at diagnosis, date of onset of symptoms, investigation and type of treatment. Results: A total of 406 cases of cervical cancer were reviewed; 233 from May – October 2019 (pre-COVID) and 173 between May – October 2020 (post COVID); representing a significant reduction in new cervical cancer diagnoses of 25% post COVID (p<0.001) There was a 42% increase in the delay from start of symptoms to diagnosis Post COVID. Pre COVID, 27% of patients presented with Stage 3 or 4 disease, whilst during COVID this was 38%; statistically significant (p <0.001). When we evaluated the treatments received between the two time periods, this was also statistically significant (chi-squared, p=0.0005). Conclusions: This study has demonstrated a statistically significant increase in the stage of cervical cancer at diagnosis and a change in treatment for cervical cancer following the onset of COVID-19. The implications of this are discussed.
Background: While pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a pre-requisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. Methods: We performed a retrospective analysis of single cell data repositories. This data was then validated at both gene and protein level by performing qRT-PCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. Findings: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels, only in the fetal intestine and kidney and is not expressed in the fetal lung. The placenta is also negative for the two proteins both during development and at term. Interpretation: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the GI tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. Funding: This work was made possible by an MRC / UKRI COVID-19 Rapid response initiative grant (MR/V028480/1).
Objective: To evaluate the efficacy of long-term indomethacin therapy (LIT) in prolonging pregnancy and reducing spontaneous preterm birth (PTB) in patients undergoing fetoscopic laser surgery (FLS) for the management of twin-to-twin transfusion syndrome (TTTS). Design: Retrospective cohort study of prospectively collected data. Setting: Collaborative multicenter study Population: 557 consecutive TTTS cases that underwent FLS Methods: LIT was defined as indomethacin use for at least 48 hours. Log-binomial regression was used to estimate the relative risk (RR) of PTB in LIT compared to non-LIT group. Cox regression was used to evaluate the association between LIT use and FLS-to-delivery survival. Main outcome measures: gestational age (GA) at delivery Results: Among the 411 pregnancies included, a total of 180 patients (43.8%) received LIT after FLS and 231 patients (56.2%) did not. Median GA at fetal intervention did not differ between groups (20.4 weeks). Median GA at delivery was significantly higher in the LIT group (33.6 weeks) compared to the non-LIT group (31.1weeks), p<0.001. FLS-to-delivery interval was significantly longer in the LIT group (P<0.001). The risk of PTB prior to 34, 32, 28, and 26 weeks gestation were all significantly lower in the LIT group compared to the non-LIT group (RR=0.69, 0.51, 0.37, and 0.18, respectively). The number needed to treat (NNT) with LIT to prevent one PTB<32 weeks gestation was 4, and to prevent one PTB<34 weeks was 5. Conclusion: Long-term indomethacin after FLS for TTTS was found to be associated with prolongation of pregnancy and reducing the risk for PTB.
Letter to editor: “Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial “Cheng-Yang Hsu1, Ching-Hu Wu1, Cheng-Yu Long1, 21 Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan2 Department of Obstetrics and Gynecology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanRunning head: Two prospective for this promising experimentWords Count: 315Corresponding Author:Dr. Cheng-Yu Long, MD, PhD, Department of Obstetrics and Gynaecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100, Shih-Chuan 1st Rd, Kaohsiung 80708, TaiwanE-mail: email@example.comDear Editor-in Chief:We read with great interest with recent publication in BJOG by Mackova et al. (1) This study describe effects of non-ablative erbium-doped: yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. The ewes were randomized to three groups: vaginal Er:YAG laser application, estrogen replacement, and sham groups.In the estrogen replacement group of ewes, an estrogen implant was inserted under the skin in the inguinal region. The result showed increase in epithelia thickness in vaginal biopsies and it was significantly higher compared with the laser application and sham groups. In all groups, the lamina propria did not showed any significant differences. Also the autopsy showed the uterus of estrogen-exposed ewes weighted more.We would like to humbly comment the vaginal estrogen use and laser application in genitourinary syndrome of menopause.The vaginal estrogen application was given twice a week with the cream in currently practice of female who suffered from genitourinary syndrome of menopause (GSM). Firstly, the vaginal estrogen application was given twice a week with the cream in clinical practice of female who suffered from GSM. The administration showed improvement of the symptoms while no significant change in serum estrogen level. (2) The estrogen implant in the ewe experiment continues to release estrogen and caused sustained estrogen effect in the ewe and caused gaining weight of uterus, which was very different with our clinical practice of intermittent vaginal cream use.Second, the application in this study is Er:YAG laser, with the the lesser wave length: 2940 nm. While the CO2 laser had much longer wave length 10600 nm and had deeper effect in not only vaginal epithelium but also lamina propia. (3) Therefore the vascularization effects of lamina propia may be obvious noticeably.We thought these 2 flaws could be revised to make the ewe experiment more accurate and similar to current management in women with GSM.ReferencesMackova KA-OX, Mazzer AM, Mori Da Cunha MA-O, Hajkova Hympanova LA-O, Urbankova IA-O, Kastelein AA-O, et al. Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial. BJOG . 2021 May;128(6):1087-1096.Long CY, Liu CM, Hsu SC, Wu CH, Wang CL, Tsai EM. A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women. Menopause . Sep-Oct 2006;13(5):737-43.Bhide AA, Khullar V, Swift S, Digesu GA. The use of laser in urogynaecology. Int Urogynecol J . 2019 May;30(5):683-692.
BJOG-20-1830.R3: The levonorgestrel intrauterine system versus endometrial ablation: when the choice of treatment goes beyond its efficacy Author: Sarah Maheux-LacroixEndometrial ablation and levonorgestrel intra-uterine system (LNG-IUS) are two well-established treatment options for women with heavy menstrual bleeding (Bergeron C, Hum Reprod Update 2020;26(2):302-11) that have contributed to the important decrease in hysterectomies over the last decades (Bergeron AM et al. J Obstet Gynaecol Can 2020;42(12):1469-74). Van den Brick et al. present a cost-effectiveness analysis comparing the two options, in which a treatment strategy starting with the LNG-IUS is less costly than a strategy starting with endometrial ablation. Up to now, economic analyzes mostly relied on simulation modeling and conclusions could vary depending on assumptions for efficacy and discontinuation in each arm. This study was based on actual data from an RCT with a 2-year follow-up.Despite the 43% discontinuation rate for LNG-IUS, this method was cheaper at 2 years and this conclusion stood up to sensitivity analyzes. The LNG-IUS remained superior despite the assumption of an ambulatory setting for endometrial ablation, but this analysis needs to be interpreted with caution. Data was lacking on costs of the outpatient setting and saving of only \euro111 was estimated when comparing to the inpatient setting (\euro2,241 versus \euro2,352). In other studies, the outpatient hysteroscopy was associated with substantial savings, being 2 to 4 times cheaper (Bennett A et al. J Obstet Gynaecol Can 2019;41(7) :930-41). Indeed, costs are always subject to vary from region to region with possibly different conclusions in different settings, but clearly an outpatient procedure reduces the cost difference between the two methods.Beyond 2 years, data is lacking. The two methods have been compared in RCT at up to 5 years (Bergeron C, Hum Reprod Update 2020;26(2):302-11) and we do not know if one method is superior the other to prevent longer term failures and re-interventions. The LNG-IUS requires replacement every 5 years but seems to decrease the risk of eventually requiring a hysterectomy in younger patient (Bergeron C, Hum Reprod Update 2020;26(2):302-11). Both factors could have an impact in a longer-term cost-effectiveness analysis and underline that future research should investigate the modifying effect of age.At the end of the day, the choice of treatment needs to be individualized to the patient needs and preferences. Certain characteristics lead us to favor the LNG-IUS, such as need for contraception, wish to preserve fertility, risk of endometrial neoplasia or presence of concomitant gynecologic conditions such as adenomyosis. On the other hand, some women do not tolerate or refuse potential side effects of hormones. Let’s keep in mind that both methods are effective, minimally invasive and represent substantial savings compared to a hysterectomy, but when both options are adequate for a patient, the LNG-IUS is less costly for society.
Title Page: MinicommentaryThis is a minicommentary on Reid et al. “How common are complications following polypropylene mesh, biological xenograft 3 and native tissue surgery for pelvic organ prolapse? A secondary analysis from the PROSPECT trial”.Title: Understanding Risk: a substitute for Information?Author : Swati Jha (MD, FRCOG)Consultant Gynaecologist and Honorary Senior Clinical Lecturer, Sheffield University. Subspecialist in UrogynaecologyInstitute : Department of Urogynaecology, Sheffield Teaching Hospitals NHS Foundation TrustAddress : Sheffield Teaching Hospitals, Level 4, Jessop Wing, Tree Root Walk, Sheffield. S10 2SFSwati.Jha1@nhs.net0044 (0)114 2268568Fax : 0114 2268165
Objective: To investigate the association between hysterectomy with conservation of one or both adnexa and ovarian and tubal cancer. Design: Prospective cohort study. Setting: 13 NHS Trusts in England, Wales and Northern Ireland. Population: 202,506 postmenopausal women recruited between 2001-2005 to the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and followed up until 31 December 2014. Methods: Multiple sources (questionnaires, hospital notes, Hospital Episodes Statistics, national cancer/death registries, ultrasound reports) were used to obtain accurate data on hysterectomy (with conservation of one or both adnexa) and outcomes censored at bilateral oophorectomy, death, ovarian/tubal cancer diagnosis, loss to follow-up or 31 December 2014. Cox proportional hazards regression models were used to assess the association. Main outcome measures: Invasive epithelial ovarian and tubal cancer (WHO 2014) on independent outcome review. Results: Hysterectomy with conservation of one or both adnexa was reported in 41,912 (20.7%; 41,912/202,506) women. Median follow up was 11.1years (IQR 9.96-12.04), totalling >2.17million women-years. Among women who had undergone hysterectomy, 0.55% (231/41912) were diagnosed with ovarian/tubal cancer, compared with 0.59% (945/160594) of those with intact uterus. Multivariable analysis showed no evidence of an association between hysterectomy and invasive epithelial ovarian/tubal cancer (RR=0.98, 95%CI 0.85-1.13, p=0.765). Conclusions: This large cohort study provides further independent validation that hysterectomy is not associated with alteration of invasive epithelial ovarian and tubal cancer risk. This data is important both for clinical counselling and for refining risk prediction models.
Objective: To estimate the effect of oestrogen-only and combined hormone replacement therapy (HRT) on the hazards of overall and age-specific all-cause mortality in healthy women aged 46 to 65 at first prescription. Design: Matched cohort study. Setting: Electronic primary care records from The Health Improvement Network (THIN) database, UK (1984−2017). Population: 105,199 HRT users (cases) and 224,643 non-users (controls) matched on age and general practice. Methods: Weibull-Double-Cox regression models adjusted for age at first treatment, birth cohort, type 2 diabetes, hypertension and hypertension treatment, coronary heart disease, oophorectomy/hysterectomy, body mass index, smoking, and deprivation status. Main outcome measures: All-cause mortality. Results: A total of 21,751 women died over an average of 13.5 years follow-up per participant, of whom 6,329 were users and 15,422 non-users. The adjusted hazard ratio (HR) of overall all-cause mortality in combined HRT users was 0.91 (95%CI 0.88−0.94), and in oestrogen-only users was 0.99 (0.93−1.07), compared to non-users. Age-specific adjusted HRs for participants aged 46-50, 51-55, 56-60, and 61-65 years at first treatment were 0.98 (0.92−1.04), 0.87 (0.82−0.92), 0.88 (0.82−0.93), and 0.92 (0.85−0.98), for combined HRT users compared to non-users, and 1.01 (0.84−1.21), 1.03 (0.89−1.18), 0.98 (0.86−1.12), and 0.93 (0.81−1.07) for oestrogen-only users, respectively. Conclusions: Combined HRT was associated with a 9% lower risk of all-cause mortality and oestrogen-only formulation was not associated with any significant changes. Funding: IFoA. Keywords: Hormone replacement therapy, menopause, mortality, primary care records, THIN. Tweetable abstract: Oestrogen-only HRT is not associated with all-cause mortality and combined HRT reduces the risks.
Objective To determine the prevalence of genital mycoplasma infection and the risk of spontaneous preterm birth (sPTB) in asymptomatic pregnant women. Design Prospective cohort. Setting Public and private health services in Ribeirão Preto-SP, Brazil. Population 1.349 asymptomatic women with a singleton pregnancy at 20-25 weeks of gestation (WG) recruited between 2010 and 2011. Methods Baseline data was assessed using a questionnaire, in addition to cervicovaginal fluid and blood samples, to analyze lower reproductive tract infections (RTIs) and immune mediators, respectively. The association between variables and the risk of sPTB was evaluated using logistic regression analysis to estimate the odds ratios (ORs). Main outcome measures Genital mycoplasma infection and prematurity. Results The prevalence of the sPTB and genital mycoplasma was 6.8% and 18%, respectively. The infection was not a risk factor for sPTB (aOR 0.66; 95% CI 0.32-1.35), even when associated with bacterial vaginosis (BV). However, it was associated with a low socioeconomic status (p=0.0470), cigarette use (p=0.0009), number of sexual partners (p=0.0019), and BV (p<.0001). Regarding the risk factors associated with sPTB, previous history of PTB (aOR 12.06; 95% CI 6.21-23.43) and a cervical length ≤ 2.5 cm (aOR 3.97; 95% CI 1.67-9.47) were significant. Conclusions The risk of sPTB was independently associated with the history of PTB and the cervical length but not with the genital mycoplasma infection. Funding: This work was founded by CNPq, FAPESP and CAPES. Keywords: Preterm birth, pregnancy, genital mycoplasma, bacterial vaginosis, risk factor
Medical Management of GDM – following the evidenceMini Commentary on 21-0353.R1 - “Changing Patterns in Medication Prescription for Gestational Diabetes During a Time of Guideline Change in the USA: A Cross-sectional Study ”Aaron B. Caughey, MD, PhDDepartment of Obstetrics and Gynecology; Oregon Health & Science University; Portland, ORCorrespondence:Aaron B. Caughey, MD, PhDProfessor and ChairDepartment of Obstetrics and GynecologyOregon Health & Sciences UniversityP: 503-494-2999F: 503-494-2391E: firstname.lastname@example.orgGestational diabetes mellitus (GDM) is one of the most common pregnancy complications and is associated with numerous pregnancy complications including preeclampsia, preterm birth, stillbirth, cesarean delivery, fetal macrosomia, birth injury, neonatal hypoglycemia, childhood obesity in the offspring and other short- and long-term complications.(Sweeting AN, et al. Diabetes Care. 2016;39:75-81) Many of these complications appear to be associated with hyperglycemia, so tight control of maternal plasma glucose is the primary approach to management during pregnancy. The first line approach is usually a strict carbohydrate-controlled diet and exercise, but when this fails, medical therapy is indicated.For many years, the first-line medical approach was injectable insulin. However, an oral hypoglycemic agent, glyburide, was increasingly adopted after a trial of glyburide versus insulin demonstrated no statistical difference in the outcomes, though it was underpowered to do so.(Langer O, et al. N Engl J Med 2000;343:1134-8) Another oral agent, metformin, was studied in an adequately powered randomized trial that found no differences in outcomes between pregnancies treated with metformin versus insulin.(Rowan JA, et al. N Engl J Med 2008;358:2003-15) Perhaps because glyburide was already being used, or that metformin crosses the placenta, or an odd finding of a higher rate of preterm birth in the metformin group, there was little adoption of metformin after this trial. Other trials of these medications have been conducted and a systematic review in 2015 demonstrated that a number of outcomes were worse in women randomized to glyburide whereas there are no differences in women randomized to metformin.(Balsells M, et al. BMJ 2015;350:h102) These findings led the American College of Obstetricians and Gynecologists (ACOG) to change their recommendations to encourage insulin to be first-line treatment in 2017.(ACOG. Obstet Gynecol. 2017;130:e17-e37) A follow-up recommendation from ACOG broadened to include metformin as well.(ACOG. Obstet Gynecol. 2018 Feb;131(2):e49-e64)So, how have these data and the recommendations from ACOG changed practice patterns? In a paper published in BJOG this month, the authors examined the pharmacologic approaches to management in GDM.(Venkatesh KK, et al. BJOG, 2021) In a large cohort of over 10,000 individuals with GDM requiring medical therapy, they found that from 2015 to 2018, the use of insulin increased from 26% to 44%, the use of metformin increased from 17% to 29%, and the use of glyburide decreased from 58% to 27%. These data are from either side of the 2017 ACOG recommendation, but end in the same year as the follow-up recommendation. Given how long it can take for recommendations to be adopted by clinicians, one wonders how the practice patterns may have continued to evolve in 2019 and 2020.Recalling that the 2017 ACOG recommendation was to have insulin be first line for GDM, while the trend is in the right direction, it was still less than 50% as of 2018. While it is understandable that clinicians and patients want to prescribe an oral agent, insulin remains an effective medication with great safety data. Likely this is why it is recommended as first-line treatment by many organizations and hopefully, further trends towards its primary use will be seen.
Objective: To compare the host and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold to the response to PP mesh in an animal model of vaginal POP surgery. Design: A study employing a sheep model Setting: KU Leuven Center for Surgical Technologies Population: 14 parous female Mule sheep Methods: P4HB scaffolds were surgically implanted in the posterior vaginal wall of sheep. The comparative PP mesh data were obtained from an identical protocol. Main outcome measures: Gross necropsy, histological and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Results: Gross necropsy revealed no implant related adverse events using P4HB scaffolds. The tensile stiffness of the P4HB explants increased at 180-days (12.498 ± 2.66 N/mm (P=0.019)) as compared to 60-days (4.585 ± 1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB scaffolds exhibited excellent tissue integration with dense connective tissue and a moderate initial host response. P4HB scaffolds induced a significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as compared to PP mesh (0.99 ± 0.78 SEM, score 0-4) at 180-days. Conclusions: P4HB scaffold facilitated a gradual load transfer to vaginal tissue over time. The fully absorbable P4HB scaffold, in comparison to PP mesh, has a favorable host response with comparable load bearing capacity. If these results are also observed at longer follow-up, a clinical study for vaginal POP surgery may be warranted to demonstrate efficacy. Key words: Pelvic organ prolapse, vaginal surgery, Poly-4-hydroxybutyrate, degradable scaffold, host response, biomechanics.
Objective To describe the characteristics and outcomes of women with inherited bleeding disorder during pregnancy and birth. Design Retrospective cohort study. Setting Tertiary care hospitals, NSW and Victoria Australia. Population 100 women with inherited bleeding disorders, who birthed 134 live infants from 132 pregnancies. Methods Data was retrospectively obtained from the patient and neonatal medical records. Descriptive analysis was used to report maternal and pregnancy characteristics, birth and neonatal outcomes. Main outcome measures Factor replacement, neuraxial analgesia use and complications, post-partum haemorrhage and neonatal complications. Results PPH occurred in 22% of deliveries with primary PPH occurring in 20% and secondary PPH in 4% of births. 48% of PPHs were classified as major. PPHs occurred across the spectrum of IBD and was evenly distributed between women who had “normalised” their factor levels in pregnancy compared to those requiring factor at the time of birth. An obstetric cause was identified in more than half of PPHs. Conclusions Women with inherited bleeding disorders can deliver safely and receive neuraxial analgesia without complication when best practices are adhered to. PPH appears to occur at higher rates than the general population despite adequate factor levels or planned replacement. Whilst an obstetric cause was demonstrable in the many cases, these findings raise concern over the current definition of “adequate” factor levels at the time of birth.
Retained Products of Conception as an Etiology for EndometritisPietro Bortoletto, MD1, Phillip A. Romanski, MD1, Nina Schatz-Siemers, DO2, Steven D. Spandorfer, MD11 The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, 1305 York Ave, 7th Floor, New York, NY 10021, USA.2 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY 10021, USA.
Objective: To estimate the association between maternal origin and obstetric anal sphincter injury (OASI), and assess if associations differed by length of residence. Design: Population-based cohort study. Setting: The Medical Birth Registry of Norway. Population: Primiparous women with vaginal livebirth of a singleton cephalic fetus between 2008 and 2017 (n=188 658). Methods: Multivariable logistic regression models estimated aORs for OASI with 95% CI by maternal region of origin and birthplace. We stratified models on length of residence and paternal birthplace. Main outcome measures: OASI. Results: Overall 6 373 cases of OASI were identified (3.4% of total cohort). Women from South Asia were most likely to experience OASI (6.2%; aOR 2.24, 95% CI 1.93–2.60), followed by those from Southeast/East Asian/Pacific (5.7%; 1.83, 1.64–2.04), and Sub-Saharan Africa (5.2%; 1.97, 1.72–2.26), compared to women originating from Norway. Among women born in the same region, those with short length of residence in Norway (0–4 years), showed higher odds of OASI. Migrant women across most regions of origin had reduced risk of OASI if they had a Norwegian compared to foreign-born partner. Conclusions: Primiparous women from Asian regions and Sub-Saharan Africa had up to two-fold risk of OASI, compared to women originating from Norway. Migrants with short residence and those with a foreign-born partner had higher risk of OASI, implying that some of the risk differential is due to sociocultural factors. Some migrants, especially new arrivals, may benefit from special attention during labour to reduce morbidity and achieve equitable outcomes.
Objective To estimate the pregnancy rates and outcomes for women with cystic fibrosis (wwCF) in the UK compared to the general population and to explore the impact of the introduction of disease modifying treatments on pregnancy rates. Design A population-based cross-sectional study. Setting Electronic records of UK CF Registry Data (~99% of all CF), and conceptions data for England and Wales (E&W). Population All women aged 15-44 years who were pregnant between 2003-2017. Methods We calculated 3-yearly crude and age-specific pregnancy rates per 1,000 women years (wys), pregnancy rates for wwCF with a G551D mutation before and after Ivacaftor was introduced in 2012 and compared live birth rates. Main outcome measures Crude rates, age specific fertility, and maternal morbidity. Results The overall pregnancy rate was 23.5 (95% CI 21.9-25.3) per 1,000 wys, ~3.4fold difference to E&W women (77.7). This pattern was evident in the age specific rates, except for those aged 40-44 years where the difference in rates was much less (wwCF 8.2 per 1,000 wys vs. 13.3 in E&W). LB rate differences mirrored pregnancy rates (wwCF 17.4 per 1000 wys vs. 61.4 E&W women). Following the introduction of Ivacaftor, pregnancy rates in wwCF with G551D increased from 29.5 to 56.9 per 1000wys (2012-2014 to 2015-2017). Conclusions Pregnancy rates in wwCF are about a third of the rates in the general population but on the rise following the introduction of Ivacaftor. There is no indication that there is a reduced chance of a live birth in wwCF who become pregnant.