Kathrine Birch Petersen

Abnormally invasive placenta-prevalence, risk factors and antenatal suspicion: results from a large population-based pregnancy cohort study in the Nordic countries.

The objective was to investigate prevalence, estimate risk factors, and antenatal suspicion of abnormally invasive placenta (AIP) associated with laparotomy in women in the Nordic countries.

The Nordic Obstetric Surveillance Study: a study of complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery

To assess the rates and characteristics of women with complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery in the Nordic countries.

Individual fertility assessment and pro-fertility counselling; should this be offered to women and men of reproductive age?

During the 1970s new contraceptive options developed and legal abortions became accessible. Family planning clinics targeting young women and men provided advice and assistance on contraception. Today, delayed childbearing, low total fertility rates and increasing use of social oocyte freezing create a need for pro-fertility initiatives. Three years ago we established a new separate unit: The Fertility Assessment and Counselling (FAC) clinic. The FAC clinic offers free individual counselling based on a clinical assessment including measurement of serum anti-Müllerian hormone and ovarian and pelvic sonography in women, sperm analysis in men, and a review of reproductive risk factors in both sexes. The FAC clinic includes a research programme with the goal to improve prediction and protection of fertility. Our first proposition is that clinics for individual assessment and counselling need to be established, as there is a strong unmet demand among women and men to obtain: (i) knowledge of fertility status, (ii) knowledge of reproductive lifespan (women) and (iii) pro-fertility advice. Addressing these issues is often more challenging than treating infertile patients. Therefore, we propose that fertility assessment and counselling should be developed by specialists in reproductive medicine. There are two main areas of concern: As our current knowledge on reproductive risk factors is primarily based on data from infertile patients, the first concern is how precisely we are able to forecast future reproductive problems. Predictive parameters from infertile couples, such as duration of infertility, are not applicable, diagnostic factors like tubal patency are unavailable and other parameters may be unsuitable when applied to the general population. Therefore, strict validation of reproductive forecasting in women and men from the general population is crucial. The second main concern is that we may turn clients into patients. Screening including reproductive forecasting may induce unnecessary anxiety through false positive predictions and may even result in overtreatment in contrast to the intended preventive concept. False negative findings may create false reassurance and result in postponement of conceptions.

Mono-ovulation in women with polycystic ovary syndrome: a clinical review on ovulation induction

Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age and is the most common cause of anovulatory infertility. The treatment approaches to ovulation induction vary in efficacy, treatment duration and patient friendliness. The aim was to determine the most efficient, evidence-based method to achieve mono-ovulation in women diagnosed with PCOS. Publications in English providing information on treatment, efficacy and complication rates were included until September 2015. Systematic reviews, meta-analyses and randomized controlled trials were favoured over cohort and retrospective studies. Clomiphene citrate is recommended as primary treatment for PCOS-related infertility. It induces ovulation in three out of four patients, the risk of multiple pregnancies is modest and the treatment is simple and inexpensive. Gonadotrophins are highly efficient in a low-dose step-up regimen. Ovulation rates are improved by lifestyle interventions in overweight women. Metformin may improve the menstrual cycle within 1-3 months, but does not improve the live birth rate. Letrozole is effective for ovulation induction, but is an off-label drug in many countries. Ovulation induction in women with PCOS should be individualized with regard to weight, treatment efficacy and patient preferences with the aim of achieving mono-ovulation and subsequently the birth of a singleton baby.

The Fertility Assessment and Counseling Clinic – does the concept work? A prospective 2‐year follow‐up study of 519 women

The Fertility Assessment and Counseling (FAC) Clinic was initiated to provide women with information about their current fertility status to prevent infertility and smaller families than desired. The aim was to study the predictive value of a risk assessment score based on known fertility risk factors in terms of time to pregnancy.

Anti-Mullerian hormone levels and fecundability in women with a natural conception

OBJECTIVES To investigate the association between anti-Müllerian hormone (AMH), a well-established marker of the ovarian reserve, and time-to-pregnancy (TTP) in natural conceptions, and to assess changes in serum-AMH in early pregnancy. STUDY DESIGN A cross sectional study comprising 279 women aged 21-42 years with a natural conception recruited during 2012-2014. AMH was measured in gestational week 10-19. AMH z-scores (z-AMH) adjusted for gestational week at blood sampling were categorised in the 1st, 2nd-4th (reference), and 5th quintile. Data were analysed by discrete-time survival-analysis and results presented as odds ratios (OR), 95% confidence interval (CI); OR <1 indicating a longer TTP and OR >1 indicating a shorter TTP. RESULTS The median AMH-level was 23.0 (range:<3.0;144.0)pmol/l, and serum-AMH decreased by 7.5% (95% CI:-12.0%;-2.8%) per gestational week. Mean±SD female age was 30.9±3.6years. The median TTP was 2 (range: 1-32) months. After adjustment for possible confounders including total sperm count, TTP was unrelated to female age (aOR:1.0, 95% CI:0.9;1.0) and continuous z-AMH (aOR:0.8, 95% CI:0.7;1.0), but women in the low z-AMH group had a shorter TTP than the reference group (aOR:1.7, 95% CI:1.1;2.7). TTP was prolonged in preconception oral contraceptive (OC) users (aOR:0.7, 95% CI:0.5;1.0, p=0.04). Compared with women having used OC <2 years, TTP was significantly longer in women having used OC for 2-12 years (aOR:0.5, 95% CI:0.2;1.0, p=0.048) and >12 years (aOR:0.4, 95% CI:0.2;0.9, p=0.022) after age-adjustment. CONCLUSIONS TTP was unrelated with z-AMH when modelled as a continuous covariate. Unexpectedly, TTP was shorter in the low z-AMH group. Natural conception was observed in women with a wide range of AMH-levels including women with undetectable serum-AMH. A continuous decrease in serum-AMH was observed during first and second trimester. Preconception OC-use was identified as an independent predictor of a prolonged TTP, and the duration of OC-use appeared to influence the delay in conception. Although this is presently one of the largest studies investigating the association between AMH and fecundability in fertile women, the study has some limitation including a relatively low participation rate and a risk of selection bias in addition to AMH assessment in pregnancy and a retrospective collection of TTP and OC-use associated with a risk of recall bias. These limitations may explain the unexpected finding of a shorter TTP in the low z-AMH group.

Investigation of anti-Müllerian hormone concentrations in relation to natural conception rate and time to pregnancy

The objectives of this study were to investigate whether anti-Müllerian hormone (AMH) concentrations can predict pregnancy rates and time to pregnancy (TTP) in women attempting to conceive naturally/having an unplanned conception, and whether there is a lower AMH threshold compatible with natural conception. This prospective cohort study included 260 women aged 25-42 years in two subcohorts: (A) healthcare workers at Rigshospitalet (2008-2010), and (B) women consulting the Fertility Assessment and Counselling Clinic (2011-2014), Rigshospitalet, Denmark. Pregnancy rates and TTP at 2-year follow-up were stratified into AMH groups: low: < 9.5 pmol/l, intermediate: 9.5-33 pmol/l, high: > 33 pmol/l. Pregnancy rates increased with increasing AMH: 60.1% (low) versus 70.0% (intermediate) versus 78.3% (high) (P = 0.03). The highest pregnancy rate (84.1%) was seen in regular cycling women with high AMH. TTP was reduced in women with high AMH compared with intermediate or low AMH (stepwise trend test P = 0.01). Natural conceptions were observed with AMH concentrations down to 1.2 pmol/l. In conclusion, high AMH, especially in ovulatory women, was associated with higher pregnancy rates. Nonetheless, TTP reflected a large variation in fecundity within similar AMH concentrations and natural conceptions occurred with AMH down to 1.2 pmol/l.

Left–right differences in ovarian volume and antral follicle count in 1423 women of reproductive age

Abstract The aim of this cross-sectional study was to investigate side differences in antral follicle count (AFC) and ovarian volume in left versus right ovaries in relation to chronological and “biological” age, the latter estimated by anti-Müllerian hormone (AMH) levels. The cohort comprised 1423 women: 1014 fertile and 409 infertile. All were examined by transvaginal sonography and serum AMH. Overall the right ovary contained 8.1% more antral follicles (p = 0.002) and had 10.7% larger volume compared with the left (p < 0.001). In all AMH quartiles, the right ovarian volume was larger than the left (p ≤ 0.003). AFC was significantly higher in the right compared to the left ovary in the three upper AMH quartiles (p ≤ 0.005). The findings were similar when stratified in age quartiles. More than half (54.8%) had polycystic ovarian (PCO) morphology in at least one ovary. Of these women, 46.3% (n = 361) had PCO morphology unilateral – most frequently on the right side (27.6%) compared to the left (18.7%, p < 0.001). The consistent difference in AFC and ovarian volume found in AMH and age quartiles may be explained by presence of a larger pool of primordial follicles in the right ovary established during fetal life.

The Nordic Obstetric Surveillance Study: A Study of Complete Uterine Rupture, Abnormally Invasive Placenta, Peripartum Hysterectomy, and Severe Blood Loss at Delivery

There is a lack of reliable research regarding severe complications at delivery, which is most likely due to the rarity of such complications. There is also the issue of interactions between different severe complications, questionable reporting, and the absence of precise terminology. The Nordic Obstetric Surveillance Study (NOSS) evaluated the rate of uterine rupture, placenta accreta, peripartum hysterectomy, and severe blood loss during delivery in Nordic countries as well as the characteristics of the women who suffered these complications. The aim was to provide valuable information that might help guide the management of obstetric emergencies. In this prospective study, the authors collected cases of severe obstetric complications from maternity units in the Nordic countries from April 2009 to August 2012. A total of 135 maternity units were included, covering 91% of all Nordic deliveries. Cases of extreme complications were reported by the clinicians at these maternity units and extracted by the authors by means of medical birth registers, hospital discharge registers, and transfusion databases. The primary outcomes examined were the rates of various complications as well as any possible risk factors among the patient population. Out of the 605,362 deliveries that took place in the participating maternity units during the study period, there were 1019 instances of complications. The rate of severe blood loss was 11.6 of 10,000 deliveries. Complete uterine rupture occurred in 5.6 of 10,000 deliveries. The rate for placenta accreta was 4.6 of 10,000 deliveries, and the rate of peripartum hysterectomy was 3.5 of 10,000 deliveries. There was only 1 maternal death. Totally, 25% of the women suffered from 2 or more complications and complications were found to be most associated with being over 35 years of age, overweight, higher parity, and having previously given birth by means of cesarean delivery. More analyses are being undertaken by the NOSS group to confirm and refine these associations. NOSS provides population-based estimates for the incidence rates and risk factors associated with various severe complications during delivery. This data set could serve as the impetus for countless new research questions that can be explored by investigators. As these complications are relatively rare, the authors stress that it is important not to rely simply on personal experience when encountering them in patients. Rather, treatment of these complications should be the product of rigorous educational efforts and organizational methods to make sure that they are addressed in the most effective ways possible.

Abnormally invasive placenta-prevalence, risk factors and antenatal suspicion

The objective was to investigate prevalence, estimate risk factors, and antenatal suspicion of abnormally invasive placenta (AIP) associated with laparotomy in women in the Nordic countries.