Nick Macklon

Nick Macklon
University of Southampton · Academic Unit of Human Development and Health

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275
Publications
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Publications

Publications (275)
Article
Full-text available
Background Freezing all embryos, followed by thawing and transferring them into the uterine cavity at a later stage (freeze-all), instead of fresh-embryo transfer may lead to improved pregnancy rates and fewer complications during in vitro fertilisation and pregnancies resulting from it. Objective We aimed to evaluate if a policy of freeze-all res...
Article
Full-text available
Study question: Is it possible to develop a patient smartphone application for Medically Assisted Reproduction (MAR) that is acceptable and feasible to patients and fertility staff? Summary answer: Staff and patients responded positively to the MediEmo smartphone application, perceiving it to be acceptable and feasible to implement in a busy clini...
Article
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Research question what are the obstetric and neonatal risks of women who conceived through frozen-thawed embryo transfer (FET) during a modified natural cycle (NC) compared to an artificial cycle (AC) method. Design we performed a follow up study of the ANTARCTICA RCT (NTR 1586) which was conducted in the Netherlands. This RCT showed that modified...
Poster
Study question: What is the association between pre-IVF success expectations and wellbeing during and after treatment? Summary answer: Patients were more optimistic than they perceived their doctors to be but this optimism was not harmful to wellbeing during or after the pregnancy test What is known already: Many professionals worry that excessi...
Article
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Study question: What is the cumulative incidence of live birth and mean time to pregnancy (by conception after IVF/ICSI or natural conception) in women experiencing unexplained recurrent implantation failure (RIF) following IVF/ICSI treatment? Summary answer: In 118 women who had experienced RIF, the reported cumulative incidence of live birth d...
Article
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Background: Despite advances in ART, implantation and pregnancy rates per embryo transfer still remain low. IVF laboratories strive to ensure that the process of handling gametes in vitro closely mimics the in vivo environment. However, there remains a lack of knowledge regarding the in vivo regulation and dynamic variation in biophysical paramete...
Article
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Recent studies suggest that elevated late follicular phase progesterone concentrations after ovarian stimulation for IVF may result in embryo–endometrial asynchrony, reducing the chance of successful implantation after fresh embryo transfer. It remains unclear to what extent elevated late follicular phase progesterone levels may occur in unstimulat...
Article
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Background: frozen–thawed embryo transfer (FET) enables surplus embryos derived from IVF or IVF-ICSI treatment to be stored and transferred at a later date. In recent years the number of FET cycles performed has increased due to transferring fewer embryos per transfer and improved laboratory techniques. Currently, there is little consensus on the m...
Article
Introduction: Until recently, limited options for preserving fertility in order to delay childbearing were available. Although egg freezing and successful thawing is now possible, it remains unclear to what extent women are aware of the availability of this technique, their attitudes towards its use, or the circumstances under which this technique...
Article
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Background: Across several European countries family formation is increasingly postponed. The aims of the study were to investigate the desire for family building and fertility awareness in the UK and Denmark. Methods: A population-based internet survey was used among women (n = 1,000) and men (n = 237) from the UK (40%) and Denmark (60%). Data...
Article
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STUDY QUESTION Are live birth rates (LBRs) after artificial cycle frozen-thawed embryo transfer (AC-FET) non-inferior to LBRs after modified natural cycle frozen-thawed embryo transfer (mNC-FET)? SUMMARY ANSWER AC-FET is non-inferior to mNC-FET with regard to LBRs, clinical and ongoing pregnancy rates (OPRs) but AC-FET does result in higher cancel...
Article
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The primary limiting factor for effective IVF treatment is successful embryo implantation. Recurrent implantation failure (RIF) is a condition whereby couples fail to achieve pregnancy despite consecutive embryo transfers. Here we describe the collection of gene expression profiles from mid-luteal phase endometrial biopsies (n = 115) from women exp...
Article
The recognition of 'fetal origins of adult disease' has placed new responsibilities on the obstetrician, as antenatal care is no longer simply about ensuring good perinatal outcomes, but also needs to plan for optimal long-term health for mother and baby. Recently, it has become clear that the intrauterine environment has a broad and long-lasting i...
Article
To assess the accuracy of antimüllerian hormone (AMH) in predicting cumulative live birth rate (CLBR) within 1 year after treatment initiation in GnRH antagonist treatment cycles for in vitro fertilization (IVF). Observational (retrospective) substudy as part of an ongoing prospective cohort study. University medical center. A total of 487 patients...
Article
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Approximately one in six couples suffer from subfertility, and many seek treatment with artificial reproductive technologies (ART). Despite improvements in laboratory techniques and ovarian stimulation, ongoing pregnancy rates per cycle remain at ~25%. Couples wanting to improve their chances may turn to adjuvant therapies, such as nutritional supp...
Article
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INTRODUCTION: Recurrent miscarriage (RM) is diagnosed when a woman has had three or more miscarriages. Increased levels of distress and anxiety are common during the waiting period of any subsequent pregnancies, posing a significant threat to psychological well-being. However, only limited support and therapy are available for these women, and many...
Article
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Do the amino acid levels of human uterine fluid vary with age, BMI, phase of menstrual cycle, benign pathology or diet? The levels of 18 amino acids in human uterine fluid were shown to be affected only by maternal diet. Murine, bovine and ovine uterine amino acid content has been reported, but no reliable data on the human exist. Murine studies ha...
Chapter
A 36-year-old woman presented with secondary infertility and secondary amenorrhea and previously diagnosed polycystic ovary syndrome. h ere were no complaints of dysfunctional blood loss, hirsutism, acne, or other endocrinological symptoms. At er failed ovulation induction with clomiphene citrate and gonadotropins, she had conceived at er IVF treat...
Article
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STUDY QUESTION What is the clinical value of anti-Müllerian hormone (AMH) for the prediction of high or low ovarian response in controlled ovarian stimulation for IVF using GnRH antagonist treatment? SUMMARY ANSWER AMH as a single test has substantial accuracy for ovarian response prediction in GnRH antagonist treatment for IVF, with a higher accu...
Article
STUDY QUESTION Does the use of a positive reappraisal coping intervention (PRCI) alone following IVF embryo transfer influence anxiety, the depression and treatment outcome when compared with its use combined with monitoring emotions, monitoring emotions alone or no intervention?
Article
Introduction: Preimplantation embryos depend on nutrients provided in the reproductive tract for development. Early human embryos have an increasing requirement for amino acids as they develop from the 1-cell through to the blastocyst stage. In vivo, the uterus provides the final environment for preimplantation development, but surprisingly, the nu...
Article
Objective: Using endometrial secretion analysis, we assessed whether altered inflammatory cytokine levels can be detected in the uterine environment in asthma patients, thereby providing a possible cause of reduced fertility in asthmatics. Methods: Forty-four unexplained infertile women (aged 28-44) underwent asthma and allergy testing, question...
Article
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Human reproduction is characterized by a high degree of embryo wastage, which is largely ascribed to a high prevalence of embryo aneuploidy. It is proposed that maternal strategies have evolved which prevent inappropriate investment in invasive, but poorly viable embryos. Key to this is the emerging concept of the endometrium as biosensor; first id...
Article
Objective To examine the effects of high-fat (HF) diet–induced maternal obesity on follicular population and gene expression in adult offspring ovaries. Design Experimental mouse study. Setting Laboratory. Animal(s) Mice on HF diet. Intervention(s) Female C57BL/6J mice were fed an HF or standard chow (C) diet 6 weeks before conception, through...
Article
Objective To assess the impact of elevated early follicular progesterone (P) levels in gonadotropin-releasing hormone (GnRH) antagonist cycles on clinical outcome using prospective data in combination with a systematic review and meta-analysis. Design Nested study within a multicenter randomized controlled trial and a systematic review and meta-an...
Article
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What is the effect of the positive reappraisal coping intervention (PRCI) on anxiety in women awaiting the outcome of an IVF/ICSI cycle? Women reported significantly more anxiety during the waiting period than before treatment, but the use of the PRCI did not significantly reduce anxiety during the waiting period. Waiting for the outcome of IVF/ICS...
Article
Objective Mental models of pregnancy refer to women's perceptions of whether their pregnancies are susceptible to poor health outcomes. Mental models influence health behaviour during pregnancy. In the present study we examined whether mental models of pregnancy are linked to compliance with folic acid supplementation guidelines. Study design Cros...
Article
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Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected embryos may fail to implant although many first breach the endometrial epithelium and embed in the decidualizing stroma before being rejected via mechanisms that are poorly understood. Here we show that developmentally impaired human embr...
Article
Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected embryos may fail to implant although many first breach the endometrial epithelium and embed in the decidualizing stroma before being rejected via mechanisms that are poorly understood. Here we show that developmentally impaired human embr...
Article
Full-text available
BACKGROUND Oocyte number is established early in life before a gradual loss of this ovarian reserve during reproductive life until oocyte availability becomes limiting at the menopause. Although there is a large genetic component to the ovarian reserve achieved before birth, other influences including the maternal endocrine and nutritional milieu,...
Article
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Study question: Whatis the impact of initiatingGnRHantagonist co-treatment for in vitro fertilization (IVF) on cycle day (CD) 2 compared with CD 6 on live birth rate (LBR) per started cycle and on the cumulative live birth rate (CLBR)? Summary answer: Early initiation of GnRH antagonist does not appear to improve clinical outcomes of IVF compared w...
Article
Implantation requires highly orchestrated interactions between the developing embryo and maternal endometrium. The association between abnormal implantation and reproductive failure is evident, both in normal pregnancy and in assisted reproduction patients. Failure of implantation is the pregnancy rate-limiting step in assisted reproduction, but, a...
Article
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BACKGROUND'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometriu...
Article
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Background: Many medical situations necessitate a stressful period of waiting for potentially threatening test results. The medical waiting period is often associated with negative anticipatory anxiety and rumination about the outcome of treatment. Few evidence-based self-help coping interventions are available to assist individuals manage these p...
Article
Although embryo implantation is essential for human survival, it remains an enigmatic biological phenomenon. Following fertilization, the resulting blastocyst must signal its presence to the mother, attach to the luminal epithelium of the endometrium and embed into the decidualising stroma. Failure to do so results in infertility, which affects aro...
Article
Objective: To compare the effect of initiating GnRH antagonist (GnRH-a) on cycle day (CD) 2 vs. CD 6 on LH, E₂, and P levels in the mid and late follicular phases. Design: Nested study within a multicenter randomized controlled trial. Setting: Reproductive medicine center in an university hospital. Patient(s): One hundred sixty patients unde...
Article
Implantation requires highly orchestrated interactions between the developing embryo and maternal endometrium. The association between abnormal implantation and reproductive failure is evident, both in normal pregnancy and in assisted reproduction patients. Failure of implantation is the pregnancy rate-limiting step in assisted reproduction, but, a...
Article
Full-text available
BACKGROUND Mechanisms underlying early reproductive loss in the human are beginning to be elucidated. The migratory and invasive capacity of human endometrial stromal cells (ESCs) is increasingly recognized to contribute to the intense tissue remodelling associated with embryo implantation, trophoblast invasion and endometrial regeneration. In this...
Article
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How do the expression patterns of neuronal markers differ in the endometrium of women with and without endometriosis? The neuronal markers, PGP9.5, NGFp75 and VR1, are expressed in the endometrium at levels that do not differ between women with and without endometriosis. Aberrant neuronal growth within the uterus may contribute to abnormal fertilit...
Article
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BACKGROUND Frozen–thawed embryo transfer (FET) enables surplus embryos derived from IVF or IVF-ICSI treatment to be stored and transferred at a later date. In recent years the number of FET cycles performed has increased due to transferring fewer embryos per transfer and improved laboratory techniques. Currently, there is little consensus on the mo...
Article
Full-text available
Sporadic miscarriage is the most common complication of early pregnancy. Two or three consecutive pregnancy losses is a less common phenomenon, and this is considered a distinct disease entity. Sporadic miscarriages are considered to primarily represent failure of abnormal embryos to progress to viability. Recurrent miscarriage is thought to have m...
Article
Implantation is an essential step in the development of a pregnancy, but often fails in humans. In assisted reproductive technologies, implantation failure continues to impair treatment outcomes, with distressing results for patients and physicians. Morphokinetics, comprehensive chromosome screening, and the analysis of embryo-derived products dete...
Article
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Implantation of a blastocyst is an absolute requirement for human reproduction. It is a complex process that involves cross-talk between the semi-allogeneic competent embryo and the receptive maternal endometrium within a transient time frame (window of implantation, WOI). Implantation can be divided into four stages: apposition, adhesion and invas...
Article
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Study question Do ART conceived singletons have significantly different hospital utilisation, costs and mortality rates compared to spontaneously conceived (SC) children during the first 5 years of life? What is the relative difference in hospital costs between singletons and multiple birth infants during the first 5 years of life?
Article
Study question Are there differences in the morphokinetics and ploidy of human embryos cultured in single versus sequential media? Summary answer The key morphokinetical parameters and percentage of euploid blastocysts are similar between the one-step culture with single continuous media and the two-step culture with sequential media. The one-step...
Article
Preconceptional health has been shown to be an important determinant of fertility, fecundity and perinatal outcomes. In recent years the impact of periconceptional factors on developmental programming, and the health of the resultant child have become increasingly clear. Since fertility specialists care for couples during this critical phase, they...
Article
Sporadic miscarriage is the most common complication of early pregnancy. Two or three consecutive pregnancy losses is a less common phenomenon, and this is considered a distinct disease entity. Sporadic miscarriages are considered to primarily represent failure of abnormal embryos to progress to viability. Recurrent miscarriage is thought to have m...
Article
Study question The aim of this study is to investigate the effect of the Positive Reappraisal Coping Intervention (PRCI) on general anxiety and depression of women awaiting the results of an IVF/ICSI treatment. Summary answer Women rated PRCI as easy to use, helpful and practical but PRCI did not have a marked effect on anxiety and depression usin...
Article
Full-text available
Study question: Are daily cycles in urinary melatonin and oxidative stress marker levels (8-hydroxydeoxyguanosine) altered in PCOS, and is this associated with changes in sleep quality? Summary answer: There is an association between elevated nighttime melatonin and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and poor sleep quality in our PCOS s...
Article
The analysis of endometrial secretions offers a window on human peri-implantation events that have hitherto been difficult to study noninvasively. Uterine secretomic analysis provides a sensitive means of interrogating the contents of secretions, which have been shown to play a key role in determining endometrial receptivity and embryo-endometrial...
Article
Full-text available
Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken...
Data
Induction of decidualization markers in hESCs and St-T1b cells. (A) Induction of transcripts for PRL, IGFBP-1 and FOXO1 upon decidualizing treatment (5d 8-Br-cAMP/MPA) was monitored by RT-PCR in two individual primary hESC cultures, and in the St-T1b human endometrial stromal cell line. (B) PRL and IGFBP-1 were measured by ELISA in culture supernat...
Data
Effect of pathway inhibitors on the appearance of St-T1b cells in chemokinetic migration. Decidualized St-T1b cells were seeded at low density in chamber slides. Following 1 h preincubation with ROCK inhibitor Y27632 (100 µM) or PI3K inhibitor Wortmannin (200 nM), monolayers were treated with control medium or PDGF-BB (10 ng/ml). Eighteen hours lat...
Data
Effect of pathway inhibitors on the appearance of hESCs in chemotactic migration assays. Decidualized hESCs in transwell migration inserts were preincubated for 1 h with MEK1/2 inhibitor PD98059 (50 µM), ROCK inhibitor Y27632 (100 µM), Rac1 inhibitor NSC23766 (50 µM), p38 inhibitor SB202190 (10 µM) or PI3K inhibitor Wortmannin (200 nM) before the a...
Data
Quantification of migrated cells in the OrisTM cell migration assay for chemokinesis. (PDF)
Article
Background The aim of this study was to understand how women with single or recurrent miscarriages cope during the waiting periods after miscarriage – waiting for pregnancy or waiting for pregnancy confirmation – and to investigate their perception of a ‘positive reappraisal’ coping intervention designed for these waiting periods. Positive reapprai...
Chapter
Ovarian stimulation is a key component of assisted conception treatments. Stimulating growth of multiple follicles enables the retrieval of many cumulus–oocyte complexes, which allows for inefficiencies of fertilization in vitro and embryo culture, enabling selection of embryos for transfer in order to increase the chance of implantation. Gonadotro...
Article
Full-text available
BACKGROUND Supportive care is regularly offered to women with recurrent miscarriages (RMs). Their preferences for supportive care in their next pregnancy have been identified by qualitative research. The aim of this study was to quantify these supportive care preferences and identify women's characteristics that are associated with a higher or lowe...
Article
Full-text available
Background: Frozen thawed embryo transfer (FET) is a cost-effective adjunct to IVF or IVF-ICSI treatment. In order to optimize treatment outcome, FET should be carried out during a period of optimal endometrial receptivity. To optimize implantation several methods for endometrium preparation have been proposed. In natural cycle FET (NC-FET), the e...
Article
Full-text available
The aetiology of recurrent miscarriage (RM) remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs) of women with RM discriminate less effectively between high...
Data
Timelapse of H-EnSCs of a woman with RM migrating towards a 3000 cell trophoblast spheroid. (MOV)
Data
Timelapse of H-EnSCs of a woman with RM migrating towards a human 3PN blastocyst. (MOV)
Article
To investigate the stability of various housekeeping genes (HKG) within healthy versus scarred peritoneal mesothelium. The use of HKG as internal controls for quantitative real-time polymerase chain reaction (qRT-PCR) studies is based on the assumption of their inherent stability. However, recent evidence suggests that this is not true for all HKG...
Article
In order to improve embryo implantation for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles the use of glucocorticoids has been advocated. It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer (NK) cell count and normalise...
Article
Despite expanding global experience with advanced reproductive technologies, the majority of IVF attempts do not result in a successful pregnancy, foremost as a result of implantation failure. The process of embryo implantation, a remarkably dynamic and precisely controlled molecular and cellular event, appears inefficient in humans and is poorly u...
Article
Thromboembolism is a rare complication of ovarian stimulation for IVF. However since venous thrombosis is a potentially serious disorder, all patients proceeding to IVF treatment should be individually assessed for their risk of thrombotic complications. As the presence of thrombophilia constitutes an important risk factor, plasma AT, proteins S an...
Article
Full-text available
Female mammals inactivate one of their two X-chromosomes to compensate for the difference in gene-dosage with males that have just one X-chromosome. X-chromosome inactivation is initiated by the expression of the non-coding RNA Xist, which coats the X-chromosome in cis and triggers gene silencing. In early mouse development the paternal X-chromosom...
Article
Full-text available
Polycystic ovary syndrome (PCOS) is a complex disorder with variable prevalence and clinical presentation in different populations, which may be mediated by geographical and ethnic background. We performed a comparison of phenotypic characteristics between 547 Chinese and 427 Dutch women with PCOS and oligo/amenorrhoea attending University Reproduc...
Article
Introduction The role of frozen-thawed embryo transfer (FET) has increased in assisted reproductive technology programs because ET policy currently favours single ET. In FET, when cryopreserved oocytes, embryos or blastocysts are thawed, there may be surplus thawed/warmed oocytes, embryos or blastocysts available after transfer. These may be refroz...
Article
Objective To analysis the alternation expression proteins profile between repeated implantation failures (RIF) group and Fertile controls (FC) during the implantation window (7 Days after LH surge). Methods Endometrial sample was collected in mid luteal phase (LH + 7) by micro biopsies (four women were selected in each group based on the histologi...
Article
Full-text available
Introduction Randomized controlled trials have shown laparoscopic removal of endometriosis to be advantageous in improving fertility outcomes for women with minimal-mild disease. There are limited data available on fertility outcomes following surgery for stage 3 and 4 endometriosis. Materials and Methods In this retrospective study at a tertiary...
Article
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Long-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown. We identified a nationwide historic cohort of 19,146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile women not treated with IVF. In 1997-1999, data on reproductive risk factors were o...