Co-treatment with letrozole during ovarian stimulation for IVF/ICSI: a systematic review and meta-analysis.

Letrozole reduces serum oestradiol by inhibiting the aromatase enzyme and has growing clinical indications in fertility. The available evidence of letrozole's role in ovarian stimulation for IVF and intracytoplasmic sperm injection (ICSI) and clinical outcomes was assessed. Medline, Cochrane, and ClinicalTrials.gov databases were systematically searched up until August 2021, including 31 studies (n = 16 randomized controlled trials [RCTs]; n = 15 observational studies). Live birth rate (LBR) in poor responders significantly increased by 7% (95% CI, 1% to 13%, P = 0.03) with letrozole co-treatment. Concomitantly, the gonadotrophin consumption was significantly reduced, without decreasing the number of retrieved oocytes. In normal responders, number of oocytes increased with 1.8 oocytes (95% CI 0.35 to 3.27, P = 0.01) with letrozole co-treatment. No significant effect on LBR, clinical pregnancy rate (CPR), or ovarian hyperstimulation syndrome rate was demonstrated. Only two studies reported on high responders and revealed no effect on LBR or CPR. Overall, the endometrium thickness was slightly affected, where as the, miscarriage rate and cancellation rate were unaffected by letrozole co-treatment. None of the included studies reported on neonatal outcomes. The quality of evidence was high or moderate in the RCTs and low in the observational studies. In conclusion, poor responders may benefit from co-treatment with letrozole during ovarian stimulation for IVF, whereas letrozole for normal and high responders requires further investigation with larger, high-quality studies.

Ovarian reserve markers after discontinuing long-term use of combined oral contraceptives.

RESEARCH QUESTION: How early do the ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) normalize after discontinuation of the long-term use of combined oral contraceptives (COC). DESIGN: This was a prospective cohort study of 68 women with a history of long-term COC use. Serum AMH concentrations, ovarian volume and AFC were measured during COC use and serially in a 4-month period after discontinuing COC: 1 and 2 weeks after discontinuation, and on cycle day 2-5 during three consecutive menstrual cycles. Changes in AMH and AFC were investigated using linear mixed models of repeated measurements adjusted for relevant covariates. RESULTS: Mean age was 29.4 years and mean duration of COC use 8.0 years. Baseline median AMH concentrations during COC use of 13 pmol/l (interquartile range [IQR] 8.4-22 pmol/l) increased to a median of 22.5 pmol/l (IQR 11-37 mol/l) 3 months after discontinuation. The estimated average increase was 53% (95% confidence interval [CI] 1.40-1.68, P < 0.001). AFC increased from a median value of 17 (IQR 11-25) to 24 (IQR 17-34). The estimated average increase was 41% (95% CI 1.30-1.52, P < 0.001). Ovarian volume increased from 2.4 to 5.8 ml (P < 0.001). The ovarian reserve markers increased continuously from baseline measurements until 2 months after discontinuation. Thereafter a plateau was reached. CONCLUSION: After discontinuation of COC, AMH increased by 53% and AFC by 41%, with values returning to normal within 2 months. This study provides clinicians with the highly relevant knowledge that AMH and AFC can be measured 2 months after discontinuation of COC without having to account for their influence.

Ovarian reserve markers and endocrine profile during oral contraception: Is there a link between the degree of ovarian suppression and AMH?

The ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) are suppressed in varying degree during the use of combined oral contraceptives (COC). Further, long-term use of COC can mask a condition of premature ovarian insufficiency. A desirable clinical tool that could distinguish true low ovarian reserve markers from COC-induced low levels during use of COC is warranted. The aim of this multicenter study including 235 COC users was to assess whether low age-adjusted AMH levels during COC use were linked to concomitant low levels of LH, FSH, estradiol and androgens - as a potential future tool to differentiate between 'false', COC-induced low AMH levels vs. true low AMH. Study population and methods: In total, 235 COC users from the general population aged 19-40 years were included. AMH, AFC and a reproductive hormonal profile were measured during COC intake. Age-adjusted AMH levels (Z-scores) were calculated from a comparison group of 983 non-users of COC. Differences in hormonal profile were tested between women with low versus high age-adjusted AMH-quartiles based on non-parametric Wilcoxon rank sum tests. The outcomes of interest were levels of gonadotropins, estradiol and androgens according to the four the age-adjusted AMH quartiles to find out if women with low age-adjusted AMH levels had a stronger gonadotropin suppression compared with women with higher age-adjusted AMH levels. Mean age of COC users was 30.2 years (SD 3.8), median AMH 14 pmol/l (inter-quartile range (IQR) 8.7-23)), median AFC 16 (IQR 11-25). We found no significant differences across the age-adjusted AMH quartiles in either the levels of gonadotropins, estrogens or androgens, respectively. Thus, the degree of suppression of FSH, LH, androgens and estradiol are unlikely to be a useful tool to differentiate between false low and true low ovarian reserve markers during COC use. Presently, there seems to be no alternative to withdrawal of the COC and to re-test the ovarian reserve after 2-3 months. Trial registration Trial no. NCT02785809 (www.clinicaltrials.gov).

Ovarian reserve markers in women using various hormonal contraceptives.

Objectives: The aim of the study was to assess whether the ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) were lower among women using the progestin-only pill (POP) or levonorgestrel-releasing intrauterine system (LNG-IUS) and similar to the decrease observed in combined oral contraceptive (COC) pill users.Methods: This retrospective study comprised 565 hormonal contraceptive users (COC, POP, LNG-IUS or contraceptive vaginal ring) and 983 non-hormonal contraceptive users, who were seen in two Danish fertility assessment and counselling clinics between 2015 and 2019. Adjusted multiple regression analysis was used to examine the differences in AMH and AFC between hormonal and non-hormonal contraceptive users.Results: Compared with non-hormonal contraceptive users, AMH was 31.1% lower among COC users [95% confidence interval (CI) -39.6%, -25.9%; p < 0.001], 35.6% lower among POP users (95% CI -49.0%, -18.6%; p < 0.001) and 17.1% lower among LNG-IUS users (95% CI -31.4%, 0.002%; p = 0.052); no significant differences were seen among vaginal ring users. Compared with non-hormonal contraceptive users, AFC was 31.3% lower among COC users (95% CI -35.0%, -25.3%; p < 0.001) and 29.7% lower among POP users (-39.1%, -17.9%; p < 0.001); no significant differences were seen among LNG-IUS or vaginal ring users. Ovarian volume was more than 50% reduced among COC and vaginal ring users (p < 0.001) but was unchanged among POP and LNG-IUS users.Conclusion: Assessment of ovarian reserve markers among users of all types of hormonal contraception should be interpreted cautiously and the type of contraceptive method considered.

Men's expectations and experiences of fertility awareness assessment and counseling.

INTRODUCTION: Men play an important role in couples' decisions about the timing of parenthood and they tend to delay parenthood. The reasons for delaying childbearing are multifaceted and complex. Their decisions may be based on a lack of accurate information about the reproductive life span and the consequences of delaying parenthood. The aim of this study was to explore men's expectations and experiences of fertility counseling. MATERIAL AND METHODS: Data were collected through semi-structured qualitative interviews with 21 men attending either the Fertility Assessment and Counseling Clinic in Copenhagen or in Horsens, Denmark. The men had no known fertility problems before going to the fertility counseling. They were interviewed before and after fertility counseling. RESULTS: The men were not concerned about their fertility before going to counseling. They believed they would be able to conceive whenever they wanted. Three of them had low semen quality and felt "punched in the gut" when they received these results at the fertility counseling. The study participants preferred clear and concrete information, and relevant knowledge at the right time was very important. The men felt empowered after the fertility counseling because they were equipped with concrete information that could inform their parenthood plans and decisions. Even the men who received unexpected bad news felt positive about the counseling. The participants perceived their knowledge and awareness of risk factors concerning fertility had increased. CONCLUSIONS: Men may benefit from an individualized approach where their fertility is assessed and they receive tailored fertility counseling specific to their personal fertility results. This type of intervention may be effective in increasing men's fertility awareness because it is personally relevant.

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

INTRODUCTION: 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. MATERIAL AND METHODS: Prospective cohort study of the first 570 women attending the FAC Clinic from 2011 to 2013 at Rigshospitalet, Denmark. A consultation included: risk assessment score sheet with items on infertility risk factors, anti-Müllerian hormone and ultrasound. The risk score was categorized as low, medium or high. After 2 years an email-based questionnaire was distributed regarding subsequent pregnancies. RESULTS: The follow-up questionnaire was answered by 519 women (91.1%). The mean age was 35 years and 38% were single at inclusion. The majority (67.8%, 352/519) tried to conceive within 2 years after attending the FAC Clinic. At follow up, 73.6% (259/352) had achieved a pregnancy, 21% (74/352) were still trying and 5.4% (19/352) had given up. Two-thirds (65%) with only low risk scores conceived spontaneously within 12 months, although this figure was only 32% for women with at least one high risk score (n = 82). Accordingly, presence of at least one high risk score reduced the odds of achieving a pregnancy within 12 months by 75% (OR 0.25, 95% CI 0.12-0.52). CONCLUSION: The new FAC Clinic concept seems usable and offers a tool for fertility experts to guide women on how to fulfill their reproductive life-plan.

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

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.

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 Impact of Suppressing Estradiol During Ovarian Stimulation on the Unsupported Luteal Phase: A Randomized Controlled Trial.

CONTEXT: Supraphysiological sex steroid levels at the follicular-luteal phase transition are implicated as the primary cause of luteal insufficiency after ovarian stimulation (OS) for in vitro fertilization. OBJECTIVE: We aimed to determine the impact of suppressing estradiol levels during OS of multiple dominant follicles on the unsupported luteal phase and markers of endometrial maturation. METHODS: At 2 university hospitals, 25 eligible egg donors were randomized to undergo OS using exogenous gonadotropins with or without adjuvant letrozole 5 mg/day. Final oocyte maturation was triggered with a GnRH agonist. No luteal support was provided. The primary outcome was the duration of the luteal phase. Secondary outcomes were luteal phase hormone profiles and the endometrial transcriptomic signature 5 days after oocyte pick up (OPU + 5). RESULTS: The median (interquartile range [IQR]) luteal phase duration was 8.0 (6.8-11.5) days compared with 5.0 (5.0-6.8) days in the intervention and control group, respectively (P < 0.001). Estradiol levels were effectively suppressed in the letrozole group with a median of 0.86 (0.23-1.24) nmol/L at OPU compared to 2.82 (1.34-3.44) nmol/L in the control group. Median (IQR) progesterone levels at OPU + 5 were 67.05 (15.67-101.75) nmol/L in the letrozole group vs 2.27 (1.05-10.70) nmol/L in the control group (P < 0.001). In the letrozole group, 75% of participants revealed endometrial transcriptomic signatures interpreted as post-receptive. In the control group, 40% were post-receptive and 50% noninformative. CONCLUSION: Suppressing estradiol levels in the follicular phase with adjuvant letrozole significantly reduces the disruption of the unsupported luteal phase after OS.

Does adjuvant letrozole reduce uterine peristalsis prior to fresh embryo transfer?

STUDY QUESTION: Does adjuvant letrozole in ovarian stimulation for IVF decrease the uterine peristalsis frequency (UPF) prior to fresh embryo transfer (ET)? SUMMARY ANSWER: Adjuvant letrozole in ovarian stimulation for IVF does not reduce the UPF significantly prior to fresh ET. WHAT IS KNOWN ALREADY: Throughout the cycle, uterine peristalsis aids spermatozoa transport to the fallopian tube and may affect implantation. At fresh ET, UPF is negatively correlated with implantation and clinical pregnancy rates and is believed to be modulated by oestradiol and progesterone. High levels of oestradiol, from multiple follicular development, in ovarian stimulation have been reported to increase UPF, whereas progesterone is considered to be an utero-relaxant. The influence of androgens is unclear. Co-treatment with letrozole during gonadotropin ovarian stimulation limits the supra-physiological oestradiol rise and may therefore reduce UPF prior to fresh ET. STUDY DESIGN SIZE DURATION: This study was carried out on subjects participating in a single-centre double-blinded randomized controlled trial of the impact of letrozole on follicle development and endocrine profiles, and investigated the impact of adjuvant letrozole in ovarian stimulation for IVF on UPF prior to fresh ET and the correlations of UPF with endocrine markers. Between 2016 and 2017, 39 women expected to be normal responders were randomized to co-treatment with letrozole or placebo. Of these, 33 women completed this element of the study. The study was carried out according to the Helsinki Declaration and the ICH-Good-Clinical-Practice. PARTICIPANTS/MATERIALS SETTING METHODS: Eligible women were randomized 1:1 to adjuvant treatment with letrozole 5 mg/day or placebo in an antagonist protocol using a fixed dose of recombinant (r) FSH 150 IU/day. Final maturation was triggered with hCG 6500 IU and luteal support with vaginal progesterone was administered from the day following oocyte aspiration. Less than 1 h prior to fresh ET, 6-min duration transvaginal ultrasound recordings of the uterus in sagittal section were performed and blood samples were drawn. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 33 women completed the study (letrozole n = 17; placebo n = 16). Age, BMI and ovarian reserve markers were similar between the groups. On the day of ET, serum oestradiol levels were significantly suppressed in the letrozole group to a mean of 867 ± 827 pmol/l compared to 3110 ± 1528 pmol/l in the placebo group (P < 0.001). Mean UPF prior to fresh ET did not differ between the intervention and placebo group (3.3 ± 0.36 versus 3.5 ± 0.51 per minute respectively, P = 0.108). UPF was assessed and agreed by two observers who were blinded to adjuvant treatment. Two patients were excluded due to poor quality of the ultrasound recordings. Supra-physiological serum oestradiol in the placebo group were negatively correlated with UPF (P = 0.014; R = -0.62), but the more physiological serum oestradiol levels in the letrozole group showed no correlation with UPF (P = 0.567; R = 0.15). Serum progesterone levels were similar in both groups and did not show any significant correlation with UPF. Testosterone levels were significantly higher in the letrozole group (P = 0.005) and showed a non-significant trend that negatively correlated with UPF in the placebo group (P-value = 0.071, R = -0.48). LIMITATIONS REASONS FOR CAUTION: Limitations of the study included the limited sample size and the lack of a power calculation specifically determined for this endpoint. WIDER IMPLICATIONS OF THE FINDINGS: The supra-physiological levels of oestradiol generated during ovarian stimulation were significantly suppressed in the intervention group. However, UPF prior to fresh ET was similar in both groups. Modulating the luteal phase sex steroids with adjuvant letrozole had little measured impact on UPF. Any beneficial effect of adjuvant letrozole during ovarian stimulation is unlikely to be due to significant modulation of UPF. STUDY FUNDING/COMPETING INTERESTS: M.D.H.'s salary was funded by an unrestricted research grant from Gedeon Richter. The expenses of the study were funded by a scientific collaboration: ReproUnion, co-financed by the European Union, Interreg Öresund-Kattegat-Skagerrak and Ferring Pharmaceuticals. The assays for the analyses were funded by Roche Diagnostics and an unrestricted research grant from Merck Life Science AS, Denmark. The authors have no competing interests to declare regarding this study. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02939898, EudraCT no.: 2015-005683-41.

Using Social Media for Qualitative Health Research in Danish Women of Reproductive Age: Online Focus Group Study on Facebook.

BACKGROUND: Social media platforms provide new possibilities within health research. With Facebook being the largest social network in the world, it constitutes a potential platform for recruitment and data collection from women of reproductive age. Women in Denmark and in other Western countries postpone motherhood and risk infertility due to their advanced age when they try to conceive. To date, no study has explored Danish women's reflections on the timing of motherhood within a social media setting. OBJECTIVE: The aim of this study was to explore the challenges and opportunities of using Facebook as a platform for qualitative health research in Danish women of reproductive age. METHODS: This study was a qualitative study based on 3 online focus groups on Facebook with 26 Danish women of reproductive age discussing the timing of motherhood in January 2020. RESULTS: Conducting online focus groups on Facebook was successful in this study as the web-based approach was found suitable for developing qualitative data with women of reproductive age and made recruitment easy and free of charge. All participants found participating in an online focus group to be a positive experience. More than half of the women participating in the online focus groups found it advantageous to meet on Facebook instead of meeting face-to-face. CONCLUSIONS: Conducting online focus groups on Facebook is a suitable method to access qualitative data from women of reproductive age. Participants were positive toward being a part of an online focus group. Online focus groups on social media have the potential to give women of reproductive age a voice in the debate of motherhood.

Are different markers of endometrial receptivity telling us different things about endometrial function?

PROBLEM: To what extent do endocrine, immunological, gene expression and histological markers of endometrial receptivity correlate? METHOD OF STUDY: Between November 2017 and September 2019, 121 women referred to a University Hospitals Fertility Clinic consented to inclusion in this cohort study. The women underwent timed endometrial biopsy followed by blood samples in a hormone-substituted cycle. Of these, 37 women had just started IVF treatment, and the remaining 84 had experienced recurrent implantation failure following IVF/ICSI. The hormone-substituted cycle consisted of initiation with oral oestradiol followed by addition of vaginal progesterone treatment for five full days. Endometrial biopsies were subject to histological examination, immune cell markers by immunohistochemistry (CD56+ , CD16+ , CD163+ , FoxP3) and gene expression microarray analyses with the endometrial receptivity array (ERA® ) test (Igenomix). Plasma progesterone and oestradiol were measured on the day of biopsy. RESULTS: CD56+ uterine natural killer (uNK) cell counts correlate with transcriptional markers of endometrial receptivity assessed by the ERA test. Endometrial maturation, receptivity and immunological markers were not correlated with mid-luteal blood plasma progesterone level. Mid-luteal serum oestradiol level correlated with markers of endometrial maturation and receptivity. The tests were carried out during a standard hormone substitution cycle, and the findings may not apply in the natural cycle. CONCLUSION: CD56+ uNK cell counts and endometrial receptivity assessed by the ERA test appear to be linked. Mid-luteal progesterone levels were not correlated to the tested markers of endometrial receptivity. In contrast, mid-luteal oestradiol level was inversely related to markers of endometrial receptivity and maturation.

Biological and Clinical Rationale for Androgen Priming in Ovarian Stimulation.

Androgen receptors are expressed by all stages of growing follicles, and follicular fluid androgen levels are positively correlated to granulosa cell androgen receptor and follicle-stimulating hormone (FSH) receptor expression. Thus, androgens may promote follicular growth, accumulation and/or responsiveness to gonadotropins. This is explored therapeutically in the concept of androgen priming, to improve the ovarian response to stimulation in assisted reproduction. Androgen effects may be achieved in two different ways, either directly by providing exogenous androgen or by providing luteinizing hormone (LH) activity [i.e., LH or human chorionic gonadotropin (hCG)] to stimulate local ovarian production of androgen. The androgen concentrations in follicular fluid by far exceed the levels in female circulation and it has recently been shown that there was no correlation between serum testosterone levels and follicular fluid androgen levels. There is some evidence that administration of exogenous dehydroepiandrosterone or testosterone increases live birth rates, but an optimal protocol has not been established and such adjuvant treatment should be considered experimental. Furthermore, studies exploring long-term administration of LH activity, achieving LH levels comparable to those seen in women with polycystic ovary syndrome, are awaited. The aim of the present review is to discuss critically the most suitable approach for androgen priming from a biological and clinical standpoint, and to evaluate current approaches and results obtained in clinical trials.

Status one year after fertility assessment and counselling in women of reproductive age-a qualitative study.

INTRODUCTION: Over the past 50 years women and men have postponed family formation in high-income societies. Fertility assessment and counselling has been suggested as a method to reduce delayed childbearing and its consequences. This study explored women's perceptions of how attending a fertility assessment intervention influenced their decisions and choices regarding family formation and childbearing. MATERIAL AND METHODS: Follow-up data from a longitudinal semi-structured qualitative interview study including 20 women aged 35-40 years seeking individual fertility counselling at the Fertility Assessment and Counselling Clinic at Rigshospitalet, Copenhagen, Denmark. The interviews were conducted one year after their consultation. Data were analysed by qualitative content analysis. RESULTS: The women perceived an increase in their knowledge after they had attended the counselling. The women saw the counselling as a catalyst for change-they changed their behaviour and relationship status. The women stopped thinking about the pros and cons of childbearing and acted instead. The women did not experience any regrets about acting. Some of the women felt that they were still in limbo as they were still in doubt concerning childbearing. The consultation had not given them an answer with a clear deadline in terms of delaying attempts to become pregnant, and this frustrated them. CONCLUSIONS: Our study highlights the impact of a fertility assessment and counselling intervention which included a perceived increase in knowledge. The clinic allows for an individualized approach to fertility awareness which is necessary given the unique nature of childbearing decisions.

Anti-Müllerian 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.

Cesarean scar pregnancy: a systematic review of treatment studies.

OBJECTIVE: To study treatment modalities for cesarean scar pregnancies (CSPs), focusing on efficacy and complications in relation to study quality. DESIGN: Systematic review. SETTING: Not applicable. PATIENT(S): A total of 2,037 women with CSP. INTERVENTION(S): Review of MEDLINE, EMBASE, and Cochrane Library to find studies including five or more women. Data were extracted on primary treatment modality/efficacy, complications, and future fertility. The level of evidence was categorized according to Oxford Centre for Evidence-based Medicine guidelines. Quality was assessed using The Cochrane Collaboration's Risk of Bias Tools for Randomized Controlled Trials and the modified Delphi techniques for case series. Meta-analysis was impossible owing to multifarious treatments. MAIN OUTCOME MEASURE(S): Successful first-line treatment. Complications were hysterectomy, laparotomy, bleeding >1,000 mL, or blood transfusion. RESULT(S): Fifty-two studies were included: four randomized, controlled trials and 48 case series. Fifteen of the 52 analyzed studies were scored as high quality. Treatment modalities were condensed to 14 different approaches. Combining study quality, level of evidence, efficacy, and safety, five approaches for treating CSP are recommended, depending on availability, severity of patient symptoms, and surgical skills: [1] resection through a transvaginal approach, [2] laparoscopy, [3] uterine artery embolization in combination with dilatation and curettage and hysteroscopy, [4] uterine artery embolization in combination with dilatation and curettage, and [5] hysteroscopy. CONCLUSION(S): This review recommends treatment options for CSP in clinical practice, based on efficacy and safety. The literature supports an interventional rather than medical approach. Present recommendations are primarily based on case series. Multicenter, well-designed studies are needed to draw definite conclusions on how to treat CSP.

Attitudes towards family formation in cohabiting and single childless women in their mid- to late thirties.

This study aimed to explore attitudes towards family formation in single or cohabiting childless women of advanced age. The design comprised semi-structured qualitative interviews of 20 women aged 34-39 years attending the Fertility Assessment and Counselling Clinic, Rigshospitalet, Copenhagen. A sample of 10 single women and 10 cohabiting women was chosen with equal distribution of postgraduate education length. Data were analysed using content analysis following the method of Graneheim and Lundman and consolidated criteria for reporting qualitative research (COREQ). The general attitude towards family formation was characterized by a fear of the consequences of choosing motherhood on one hand, and a 'ticking biological clock' and a wish to establish a nuclear family on the other. The women idealized the perception of perfect mothering in terms of uncompromising expectations of child rearing and showed an increasing awareness of solo motherhood as a possible solution to advanced age, the wish of a child and single status compared to earlier studies. Our study contributes to knowledge and understanding of personal considerations related to childbearing in nullipara women in their mid- to late 30s and may be useful in a fertility assessment and counselling setting.