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Aim To evaluate the effects of offering a clinic-driven lifestyle intervention programme in the waiting time before fertility treatment to women and men with obesity (body mass index [BMI] ≥ 30 kg/m2). Methods This prospective intervention study was conducted at a public Danish fertility clinic. All consecutive patients, both women and men, referred to the clinic between May 2020 and March 2021 with a BMI ≥ 30 kg/m2 were offered a 6-month lifestyle intervention programme consisting of monthly motivational dialogues and counselling with a certified nutritionist nurse. Weight loss maintenance was evaluated at a 1-year follow-up visit conducted 6-months after completion of the programme. The primary outcomes were absolute weight loss (kg) and relative weight loss (percent compared with weight at inclusion) upon completing the 6-month programme and at the 1-year follow-up. Secondary outcome measures were effects on biochemical metabolic markers. Results Forty-five participants were enroled in the study, of which 38 completed the 6-months lifestyle intervention programme and 33 participated in the 1-year follow-up. The participants' mean weight loss was 5.4 kg (95% confidence interval [CI]: 3.3, 7.5) after the 6-month programme (30 of 38 participants lost weight) and 4.4 kg (95% CI: 1.4, 7.3) at the 1-year follow-up compared with baseline. Previously undiagnosed metabolic conditions were revealed in 61% of the participants, including four cases (11%) of undiagnosed diabetes mellitus type 2. Conclusion A clinic-driven lifestyle intervention programme offered to patients with obesity in the waiting time for fertility treatment can successfully reduce weight in a high number of patients with stable results at 1-year follow-ups. Metabolic conditions, including diabetes mellitus type 2, are likely underdiagnosed in this group of patients, but further studies are needed., Aim To evaluate the effects of offering a clinic-driven lifestyle intervention programme in the waiting time before fertility treatment to women and men with obesity (body mass index [BMI] ≥ 30 kg/m2). Methods This prospective intervention study was conducted at a public Danish fertility clinic. All consecutive patients, both women and men, referred to the clinic between May 2020 and March 2021 with a BMI ≥ 30 kg/m2 were offered a 6-month lifestyle intervention programme consisting of monthly motivational dialogues and counselling with a certified nutritionist nurse. Weight loss maintenance was evaluated at a 1-year follow-up visit conducted 6-months after completion of the programme. The primary outcomes were absolute weight loss (kg) and relative weight loss (percent compared with weight at inclusion) upon completing the 6-month programme and at the 1-year follow-up. Secondary outcome measures were effects on biochemical metabolic markers. Results Forty-five participants were enroled in the study, of which 38 completed the 6-months lifestyle intervention programme and 33 participated in the 1-year follow-up. The participants' mean weight loss was 5.4 kg (95% confidence interval [CI]: 3.3, 7.5) after the 6-month programme (30 of 38 participants lost weight) and 4.4 kg (95% CI: 1.4, 7.3) at the 1-year follow-up compared with baseline. Previously undiagnosed metabolic conditions were revealed in 61% of the participants, including four cases (11%) of undiagnosed diabetes mellitus type 2. Conclusion A clinic-driven lifestyle intervention programme offered to patients with obesity in the waiting time for fertility treatment can successfully reduce weight in a high number of patients with stable results at 1-year follow-ups. Metabolic conditions, including diabetes mellitus type 2, are likely underdiagnosed in this group of patients, but further studies are needed.

STUDY QUESTION: What are the downstream endocrine and paracrine consequences of letrozole (LZ) cotreatment during ovarian stimulation and is follicle growth and recruitment affected? SUMMARY ANSWER: Letrozole cotreatment induces marked changes in both the follicular and luteal phase endocrinology causing potentiation of follicle diameter and an improved corpus luteum function without affecting the secondarily recruited follicle cohort. WHAT IS KNOWN ALREADY: Letrozole is a third-generation aromatase inhibitor that is well-established as an effective ovulatory agent, while its possible benefits in standard in vitro fertilization protocols are less thoroughly investigated. STUDY DESIGN, SIZE, DURATION: This study included a double-blinded, placebo-controlled, randomized study with LZ or placebo intervention during ovarian stimulation for IVF treatment, an observational preceding baseline natural cycle and a succeeding follow-up visit. Participants were enrolled between August 2016 and November 2018. Data from the randomized, stimulated cycle were part of a larger RCT, which was previously published. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a public fertility clinic at Herlev Hospital, Denmark, including 31 healthy, normo-responding women eligible for IVF treatment. They underwent a natural baseline cycle and were subsequently randomized to receive either LZ 5 mg (n = 16) or placebo (n = 15) daily during ovarian stimulation from cycle day (CD) 2-3 until induction of ovulation. Throughout both cycles, monitoring was performed every third day with transvaginal ultrasound for assessment of follicle count and diameter, and blood analyses for the determination of twelve endocrine and paracrine parameters. A follow-up assessment was performed at CD2-3 in the succeeding cycle. In the randomized part of the study, we determined differences in blood parameters, follicle recruitment, and follicle diameter. In the observational part of the study, we

STUDY QUESTION: Is human leukocyte antigen (HLA)-F protein expressed in mid-secretory endometrium, and are its expression levels influenced by HLA-F gene polymorphisms and correlated with the abundance of uterine natural killer (uNK) cells and anti-inflammatory M2 macrophages? SUMMARY ANSWER: HLA-F protein is expressed in mid-secretory endometrium, and levels are correlated with immune cell infiltration, plasma progesterone concentrations and HLA-F single-nucleotide polymorphisms (SNPs), however, women experiencing recurrent implantation failure (RIF) show differences when compared to women attending their first IVF treatment. WHAT IS KNOWN ALREADY: The immunomodulatory HLA class Ib molecules HLA-G and HLA-F are expressed on the extravillous trophoblast cells and interact with receptors on maternal immune cells. Little is known regarding HLA-F expression in endometrial stroma and HLA-F function; furthermore, HLA-F and HLA-G SNP genotypes and haplotypes have been correlated with differences in time-to-pregnancy. STUDY DESIGN, SIZE, DURATION: Primary endometrial stromal cell (ESC) cultures (n ¼ 5) were established from endometrial biopsies from women attending IVF treatment at a fertility clinic. Basic HLA-F and HLA-G protein expression by the ESCs were investigated. A prospective controlled cohort study was performed including 85 women with a history of RIF and 36 control women beginning their first fertility treatment and with no history of RIF. In some analyses, the RIF group was divided into unknown cause, male infertility, female infertility, and both female and male infertility. Endometrial biopsies and blood samples were obtained the day equivalent to embryo transfer in a hormone-substituted cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: HLA protein expression by ESCs was characterized using flow cytometry and western blot. In the cohort study, the specific immune markers HLA-F and HLA-G, CD56 and CD16 (NK cells), CD163 (M2 macrophages), FOXP3 (regulatory

Objective Maternal overweight and obesity during pregnancy increases the risk of large-for-gestational age (LGA) birth and childhood obesity. We aimed to investigate the association between maternal weight change between subsequent pregnancies and risk of having a LGA birth. Design Population-based cohort. Setting Routinely collected antenatal healthcare data between January 2003 and September 2017 at University Hospital Southampton, England. Participants Health records of women with their first two consecutive singleton live-birth pregnancies were analysed (n=15 940). Primary outcome measure Risk of LGA, recurrent LGA and new LGA births in the second pregnancy. Results Of the 15 940 women, 16.0% lost and 47.7% gained weight (≥1 kg/m 2) between pregnancies. A lower proportion of babies born to women who lost ≥1 kg/m 2 (12.4%) and remained weight stable between-1 and 1 kg/m 2 (11.9%) between pregnancies were LGA compared with 13.5% and 15.9% in women who gained 1-3 and ≥3 kg/m 2, respectively. The highest proportion was in obese women who gained ≥3 kg/m 2 (21.2%). Overweight women had a reduced risk of recurrent LGA in the second pregnancy if they lost ≥1 kg/m 2 (adjusted relative risk (aRR) 0.69, 95% CI 0.48 to 0.97) whereas overweight women who gained ≥3 kg/m 2 were at increased risk of new LGA after having a non-LGA birth in their first pregnancy (aRR 1.35, 95% CI 1.05 to 1.75). Normal-weight women who gained weight were also at increased risk of new LGA in the second pregnancy (aRR 1.26, 95% CI 1.06 to 1.50 with gain of 1-3 kg/m 2 and aRR 1.34, 95% CI 1.09 to 1.65 with gain of ≥3 kg/m 2). Conclusions Losing weight after an LGA birth was associated with a reduced LGA risk in the next pregnancy in overweight women, while interpregnancy weight gain was associated with an increased new LGA risk. Preventing weight gain between pregnancies is an important measure to achieve better maternal and offspring outcomes.

Over the last decade the use of frozen-thawed embryo transfer has substantially increased, and currently up to one in two embryos transferred has been cryopreserved. To support implantation, endometrial and embryo maturity are required to be synchronized. This can be achieved in various ways. The most commonly applied endometrial preparation methods are the "natural cycle," in which the sequential estrogen and P necessary for endometrial maturation are derived from the developing follicle, and the "artificial" cycle, in which these are sequentially administered. Review of the published data comparing these approaches does not identify a superior approach in terms of clinical outcomes. However, although the "natural cycle" avoids the need for luteal support, the artificial cycle provides more control over timing of ET, and the "modified" natural cycle, in which ovulation is triggered exogenously, may offer both of these advantages. The optimal monitoring strategy for freeze-thaw cycles remains unclear, because only a few studies have addressed this question. Further studies are also required to determine the ideal dosage, method of administration, and duration of estrogen and P supplementation in artificial cycle frozen embryo transfer.