Michelle Lane

Monash IVF Group · Research and Development

Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage. Since sperm DNA damage may reduce embryo quality and increase miscarriage rates, it is possible that untreated sperm oxidative stress may impair in vitro fertilization (IVF) live birth rates. Given that the antioxidant Menevit is reported to reduce spe...

Male obesity, which often co-presents with micronutrient deficiencies, is associated with sub-fertility. Here we investigate whether short-term dietary supplementation of micronutrients (zinc, selenium, lycopene, vitamins E and C, folic acid, and green tea extract) to obese mice for 12 days (designed to span the epididymal transit) could improve sp...

Blastocyst culture and transfer for human IVF has resulted in an increase in implantation and live birth rates and successfully facilitated the move toward single embryo transfer. Initially this was attained through the development and introduction of sequential media, designed to mirror the changing nutritional environments within the oviduct and...

The detrimental consequences of obesity on female fertility are well known, but the functional changes that occur in the ovary in response to elevated BMI are not clear. Obesity induces multiple components of a systemic inflammatory state that is a key pathway by which it initiates tissue dysfunction in adipose, liver and muscle; however whether ob...

Purpose: Mild controlled ovarian hyperstimulation (COH), combined with oocyte retrieval (OR) under local anaesthesia (LA), may provide low-impact IVF. Since a single injection of corifollitrophin alfa (CFA) provides 7 days of COH, we hypothesised that clomiphene-citrate (CC) followed by CFA may provide adequate COH response from one single FSH inj...

Most of the Australian 'old endemic' rodents have greatly reduced distributions with several species now threatened with extinction. Application of assisted reproductive technology has the potential to assist in their conservation programs in at least a few species. Here we describe an attempt to cryopreserve spermatozoa from two of these species -...

Purpose: The purpose of this study is to determine if there is an additive effect of combined advanced maternal and paternal age on pregnancy and live birth rates. Methods: Retrospective data analysis of 4057 first cycles at a fertility centre between 2009 and 2013 was compiled. Donor, preimplantation genetic screening and double embryo transfer...

There is growing evidence from animal and human studies that demonstrate that acquired paternal traits can impair both a male's fertility and the health of his offspring, including advanced age, smoking, stress, trauma, under-nutrition, infection, toxin exposure, and obesity. Curiously, many of these factors manifest as impaired neurological, behav...

Paternal obesity programs metabolic syndrome in offspring. Low-impact exercise in obese males improves the metabolic health of female offspring, however whether this occurred in male offspring remained unknown. C57BL/6NHsd (Harlan) mice were fed a control diet (CD; 6% fat, n = 7) or a high-fat diet (HFD; 21% fat, n = 16) for 18 weeks. After 9 weeks...

Gene expression and/or epigenetic deregulation may have consequences for sperm and blastocysts, as well as for the placenta, together potentially contributing to problems observed in offspring. We previously demonstrated specific perturbations of fertilization, blastocyst formation, implantation, as well as aberrant glucose metabolism and adiposity...

The prevalence of obesity is increasing worldwide and has tripled in men of reproductive age since the 1970s. Concerningly, obesity is not only comorbid with other chronic diseases, but there is mounting evidence that it increases the non-communicable disease load in their children (eg mortality, obesity, autism). Animal studies have demonstrated t...

The physical and nutritional environment experienced by the mother prior to and during conception is imperative to the outcome of pregnancy and offspring health. In addition, there is now mounting evidence that paternal exposures and conditions at the time of conception are also an important determinant of pregnancy outcome and offspring health. Sp...

The degree of differential expression in a HFD father’s sperm of 371 mouse quality detectors that were ranked using LIMMA in R. (XLSX)

Sperm microRNA expression in an expanded group from 3 cohorts of CD or HFD fed fathers (CD n = 13; HFD n = 14) as determined by qPCR. (DOCX)

Mean Cts for 53 mouse sperm microRNAs that were only detected in either in CD or HFD fed father's sperm. (XLSX)

The 311 experimentally validated mRNA targets of the 13 sperm microRNAs with differential abundance due to a father’s HFD and the microRNAs which target them. (XLSX)

Objective: To assess the contribution of maternal factors to major birth defects after in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and natural conception. Design: Retrospective cohort study in South Australia for the period January 1986 to December 2002. Setting: A whole of population study. Population: A census of...

There is an ever increasing body of evidence that demonstrates that paternal over-nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether paternal under-nutrition can also program impaired health in offspring and if any detrimental health outcomes in offspring could be prevented by micronutrient suppl...

This systematic review investigated the effect of paternal obesity on reproductive potential. Databases searched were Pubmed, Ovid, Web of Science, Scopus, Cinahl and Embase. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Outcomes were: likelihood of infertility, embryo development, clinical pr...

The prevalence of overweight and obesity in reproductively aged adults is increasing worldwide. While the effects of either paternal or maternal obesity on gamete health and subsequent fertility and pregnancy have been reported independently, the combination of having both parents overweight/obese on fecundity and offspring health has received mini...

To investigate the impacts that a paternal high fat diet (HFD) has on embryology, ovarian/cumulus cell gene expression and COC metabolism from female offspring, using a mouse model. Founder male mice were either fed a control diet (CD) or a HFD for 12 weeks. The HFD induced obesity but not diabetes, and founder males were then mated to normal weigh...

Obesity and related comorbidities are becoming increasingly prevalent globally. In mice preconception paternal exposure to a high fat diet (HFD) impairs the metabolic and reproductive health of male offspring, despite their control diet (CD) consumption. However, offspring share lifestyle, including diet, with parents. We assessed if male offspring...

The peri-conceptual environment represents a critical window for programming fetal growth trajectories and susceptibility to disease however the underlying mechanism responsible for programming remains elusive. This study demonstrates a causal link between reduction of pre-compaction embryonic mitochondrial function and perturbed offspring growth t...

Obesity and type II diabetes are increasingly prevalent across all demographics. Paternal obesity in humans and rodents can program obesity and impaired insulin sensitivity in female offspring. It remains to be determined whether these perturbed offspring phenotypes can be improved through targeted lifestyle interventions in the obese father. Using...

The prevalence of overweight and obesity in reproductive-aged men is increasing worldwide, with >70% of men >18 years classified as overweight or obese in some western nations. Male obesity is associated with male subfertility, impairing sex hormones, reducing sperm counts, increasing oxidative sperm DNA damage and changing the epigenetic status of...

The concept of non-genetic inheritance is gaining considerable attention in the assisted reproductive technology (ART) community due to the reported differences between children born from ART and those that are conceived naturally. It has been demonstrated that children conceived via ART have differences in fetal growth, birth weight, congenital ab...

The field of modern embryo culture spans several decades. However, in the last decade of the 20th century a resurgence of interest in embryo physiology and metabolism led to highly significant improvements in embryo culture conditions. It also became apparent that for successful development of viable mammalian embryos in vitro, one needs to underst...

Maternal over-nutrition during pregnancy is a risk factor for pregnancy complications and is increasingly associated with adverse childhood outcomes such as increased propensity for obesity and metabolic disease. However, there is emerging evidence that parental lifestyle factors prior to and at conception have a powerful impact on the health of th...

Background: The global rates of male overweight/obesity are rising, approaching 70% of the total adult population in Western nations. Overweight/obesity increases the risk of chronic diseases; however, there is increasing awareness that male obesity negatively impacts fertility, subsequent pregnancy, and the offspring health burden. Developmental...

Studies of selenium (Se) status indicate that Se is necessary for fertility but how precisely is not known. We aimed to show that Se was important in bovine female reproductive function. The elemental distribution in the bovine ovary (n = 45 sections) was identified by X-ray fluorescence (XRF) imaging. Se was consistently localized to the granulosa...

At fertilization, the gametes endow the embryo with a genomic blueprint, the integrity of which is affected by the age and environmental exposures of both parents. Recent studies reveal that parental history and experiences also exert effects through epigenomic information not contained in the DNA sequence, including variations in sperm and oocyte...

Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS) are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investiga...

Objective To determine whether supplementation of embryo culture media with a substrate to stimulate mitochondrial activity improves embryo viability and pregnancy establishment in aged mice. Design Female mice were superovulated and mated. Zygotes were collected and cultured in either G1/G2 or G1/G2 with 1.0 mM dichloroacetic acid (DCA), a stimul...

Is the activity of sirtuin 3 (SIRT3) altered in granulosa and cumulus cells from young women with reduced ovarian reserve or women of advanced maternal age? SIRT3 mRNA and active protein in granulosa and cumulus cells were decreased in women with reduced ovarian reserve and advanced maternal age. Young women with reduced ovarian reserve or women of...

To determine whether dietary and exercise regimes in obese males can provide a novel intervention window for improving the reproductive health of the next generation. Experimental animal study. University research facilities. C57BL6 male and female mice. Mice were fed a control diet (6% fat) or high-fat diet (21% fat) for 9 weeks. After the initial...

Since the inception of modern embryo culture media over 50 years ago there have been significant developments in culture systems for the mammalian preimplantation embryo. Carbohydrate gradients have been shown to impact embryo physiology and viability, while amino acids have been determined to have specific temporal effects during the preimplantati...

Introduction The introduction of amino acids to the culture media for the mammalian oocyte and embryo is arguably the most important advance made in regards to the successful culture of viable embryos. Currently all media for the culture of human embryos contain amino acids as a core component of their formulation. Amino acids are molecules contain...

Women with reduced ovarian reserve or advanced maternal age have an altered metabolic follicular microenvironment. As sirtuin 5 (SIRT5) senses cellular metabolic state and post-translationally alters protein function, its activity may directly impact on oocyte viability and pregnancy outcome. Therefore, we investigated the role of SIRT5 in relation...

Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. He...

Composition of Animal Diets. (DOC)

Correlations of Founder Metabolism on Blastocyst and Fetal Health Independent of Founder Adiposity. (DOC)

The Effect of Diet and Exercise on Founder Male Serum Metabolites after Intervention. (DOC)

Numbers of Embryos and Pups Derived from each Father. (DOC)

The Effect of Diet and Exercise on Founder Male Body Composition after Intervention. (DOC)

The capacity to be able to rank embryos in a quantitative fashion in the laboratory is highly sought after with many different approaches being tried, both refining morphological assessments that have been used for many years as well as the development and adoption of new technologies either genomic, transcriptomic, proteomic, and metabolic approac...

To assess the relative success of morula and early blastocyst slow freezing and vitrification in regards to survival and implantation rates utilising protocols which could be clinically implemented as a viable alternative to expanded blastocyst stage freezing. Mouse morula and early blastocysts were either slow frozen/thawed or vitrified/warmed. Th...

Obesity is highly prevalent, and its incidence is increasing. The previous study showing a major effect of paternal obesity on metabolic health of offspring is confounded by comorbidity with diabetes. Therefore, we investigated the effect of diet-induced paternal obesity, in the absence of diabetes, on the metabolic health of two resultant generati...

Human embryos donated for embryonic stem cell (ESC) derivation have often been cryopreserved for 5-10 years. As a consequence, many of these embryos have been cultured in media now known to affect embryo viability and the number of ESC progenitor epiblast cells. Historically, these conditions supported only low levels of blastocyst development nece...

Purpose: Embryos generated from oocytes which have been vitrified have lower blastocyst development rates than embryos generated from fresh oocytes. This is indicative of a level of irreversible damage to the oocyte possibly due to exposure to high cryoprotectant levels and osmotic stress. This study aimed to assess the effects of vitrification on...

Human embryos for hESC derivation are often donated at the cleavage stage and of reduced quality. Poor quality embryos have lower efficiency for hESC derivation. However, cleavage stage mouse embryos develop into higher quality expanded blastocysts if they are cultured with insulin, suggesting that this approach could be used to improve hESC deriva...

Male obesity in reproductive-age men has nearly tripled in the past 30 y and coincides with an increase in male infertility worldwide. There is now emerging evidence that male obesity impacts negatively on male reproductive potential not only reducing sperm quality, but in particular altering the physical and molecular structure of germ cells in th...

Obesity and other related conditions, such as type 2 diabetes, are becoming increasingly prevalent. It has been previously shown in rodents that a chronic paternal exposure to a high fat diet (HFD) induces altered glucose homeostasis and obesity, subsequently giving rise to glucose intolerance in female F1 offspring. Here we show that a mouse model...

Male obesity is now known to impact negatively on male reproductive potential by affecting the molecular and physical struture of sperm, as well as the developing fetus and health of subsequent offspring. With a recent human study reporting that children from obese fathers were more likely to be overweight or obese themselves. Whether interventions...

Obesity and adverse related conditions, notably type 2 diabetes and sub-fertility are increasingly prevalent. It is now clear that the origins of developmental programming in the offspring originate not only from the mother but also from the father. Reports from our laboratories and others have now demonstrated a transmission of nutritional cues fr...

The preparation of defined culture media for embryo development has progressed from simple chemically defined media based on Krebs-Ringer bicarbonate, supplemented with glucose, bovine plasma albumin, antibiotics and utilizing a CO(2)-bicarbonate buffering system to more complete systems based around studies on the physiology and metabolism of the...

To determine whether altered follicular environment is associated with ovarian reserve or maternal age. Prospective study examining follicular fluid (FF) composition and follicular cell metabolism. University research department and private IVF clinic. Women (n = 54) undergoing routine IVF treatment were allocated to one of three groups based on ov...

The increasing prevalence of obesity in women of child-bearing age is of growing concern in the health community. Obesity is associated with sub-optimal reproductive performance; therefore, it is understandable that the number of young women with elevated body mass index (BMI) accessing assisted reproductive treatment (ART) is on the rise. Conseque...

To determine whether the high lipid content of human follicular fluid influences oocyte maturation. Mouse oocytes as substitutes for human oocytes were exposed to follicular fluids of differing lipid content with outcome monitoring. Private infertility clinic and university laboratory. Seventy-four women seeking assisted reproduction, and gonadotro...

With the advent of culture media based upon the nutrient composition of the human oviduct and uterus, and specifically designed to support the human embryo in vitro, it has become feasible to culture the pronucleate oocyte to the blastocyst stage as a routine procedure in human IVF. The potential advantages of extended culture go beyond increases i...

Obesity and related conditions, notably subfertility, are increasingly prevalent. Paternal influences are known to influence offspring health outcome, but the impact of paternal obesity and subfertility on the reproductive health of subsequent generations has been overlooked. A high-fat diet (HFD) was used to induce obesity but not diabetes in male...

High-quality embryos give rise to embryonic stem cells (ESCs) at greater efficiencies than poor-quality embryos. However, most embryos available for human ESC derivation are of a reduced quality as a result of culture in relatively simple media up to 10 years earlier, before cryopreservation, or before compaction. In the present study, we used a mo...

Male obesity is associated with reduced sperm motility and morphology and increased sperm DNA damage and oxidative stress; however, the reversibility of these phenotypes has never been studied. Therefore, the aim of this study was to assess the reversibility of obesity and its associated sperm physiology and function in mice in response to weight l...

Although obvious effects of obesity on female reproduction and oocytes are emerging, the effects on male fertility and sperm quality are less clear with studies reporting conflicting results. We hypothesize that male obesity affects sperm function and physiology probably as a result of elevated oxidative stress in spermatozoa and therefore elevated...

Male obesity is associated with reduced sperm function and increased incidence of sperm DNA damage; however, the underlying molecular mechanisms have not yet been identified. Mammalian SIRT6 protein is involved in caloric-dependant DNA damage repair in other tissue types, yet a possible role for SIRT6 in male obesity and subfertility has not been i...

Introduction Transfer of more than a single embryo in an IVF cycle carries with it the finite probability of a multiple gestation. With the advent of more physiological laboratory procedures and culture systems, implantation rates have improved significantly over the past decade resulting in the ability to transfer single embryos, while maintaining...

Introduction The ovarian follicle provides nutrients and hormonal signals critical for normal maturation of the oocyte and its competence to develop into a healthy embryo. Previous studies from our laboratory have shown that the follicular environment of obese women is altered compared to that of moderate weight women; in particular follicle fluid...

The optimal outcome after IVF is a live, healthy, singleton term baby. This can be achieved by transferring a single embryo, but at the possible expense of reducing pregnancy rates. Recent studies suggest that delaying transfer of embryos to the blastocyst stage (day 4/5), rather than the more traditional cleavage stage (day 2-3), allows for better...

Environmental stress results in perturbations to mitochondrial function in the preimplantation embryo and hinders subsequent embryo and possibly offspring development. Global gene expression in fetal mouse brain was investigated following targeted mitochondrial inhibition by amino-oxyacetate (AOA) from the 2-cell to the blastocyst stage. Blastocyst...

To identify the cumulus cell gene expression associated with oocyte developmental competence, specifically live birth, after single ET (SET) assisted reproductive technology. Retrospective gene expression analysis in human cumulus cells from oocytes that established a pregnancy resulting in live birth versus no pregnancy after SET. Independent IVF...

The aim of this study was to determine the relationship between nutrient utilization by the human embryo and its subsequent viability after transfer. METHODS The embryos of 50 patients having single blastocyst transfer were cultured individually from Day 3 in 10 µl drops of medium G2 under Ovoil in 5%O(2), 6%CO(2), 89%N(2). Patient inclusion in the...

Oocyte in vitro maturation (IVM) reduces the need for gonadotrophin-induced ovarian hyperstimulation and its associated health risks but the unacceptably low conception/pregnancy rates have limited its clinical uptake. We report the development of a novel in vitro simulated physiological oocyte maturation (SPOM) system. Bovine or mouse cumulus-oocy...