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Journal: Reproductive biomedicine online


Experimental ooplasmic transplantation from donor to recipient oocyte took place between 1996 and 2001 at Saint Barnabas Medical Center, USA. Indication for 33 patients was repeated implantation failure. Thirteen couples had 17 babies. One patient delivered twins from mixed ooplasmic and donor egg embryos. A limited survey-based follow-up study on the children is reported: 12 out of 13 parents completed a questionnaire on pregnancy, birth, health, academic performance and disclosure. Parents of a quadruplet did not participate. Prenatal development and delivery were uneventful. School grades ranged from good to excellent. Children were of good health. Body mass index (BMI) was normal in 12 out of 13 children. One child had chronic migraine headaches, two mild asthma, three minor vision and three minor skin problems. One boy from a boy/girl twin was diagnosed with borderline pervasive developmental disorder - not otherwise specified at age 18 months, but with no later symptoms. One couple disclosed the use of egg donor to their child. One reported intention to disclose; six were undecided and four reported they would not disclose. This limited follow-up strategy presents a high risk of bias. Parents may not assent to standardized clinical analysis owing to lack of disclosure to their children.

Concepts: Pregnancy, Childbirth, Asthma, Embryo, Body mass index, Pervasive developmental disorder, Implantation, Zygote


Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. The severity of clinical symptoms is often associated with the level of mtDNA mutation load or degree of heteroplasmy. Current clinical options to prevent transmission of mtDNA mutations to offspring are limited. Experimental spindle transfer in metaphase II oocytes, also called mitochondrial replacement therapy, is a novel technology for preventing mtDNA transmission from oocytes to pre-implantation embryos. Here, we report a female carrier of Leigh syndrome (mtDNA mutation 8993T > G), with a long history of multiple undiagnosed pregnancy losses and deaths of offspring as a result of this disease, who underwent IVF after reconstitution of her oocytes by spindle transfer into the cytoplasm of enucleated donor oocytes. A male euploid blastocyst wasobtained from the reconstituted oocytes, which had only a 5.7% mtDNA mutation load. Transfer of the embryo resulted in a pregnancy with delivery of a boy with neonatal mtDNA mutation load of 2.36-9.23% in his tested tissues. The boy is currently healthy at 7 months of age, although long-term follow-up of the child’s longitudinal development remains crucial.

Concepts: DNA, Pregnancy, Mitochondrion, Mitochondrial DNA, Meiosis, Zygote, Human mitochondrial genetics, Mitochondrial disease


Male infertility constitutes 30-40% of all infertility cases. Some studies have shown a continuous decline in semen quality since the beginning of the 20th century. One postulated contributing factor is radio frequency electromagnetic radiation emitted from cell phones. This study investigates an association between characteristics of cell phone usage and semen quality. Questionnaires accessing demographic data and characteristics of cell phone usage were completed by 106 men referred for semen analysis. Results were analysed according to WHO 2010 criteria. Talking for ≥1 h/day and during device charging were associated with higher rates of abnormal semen concentration (60.9% versus 35.7%, P < 0.04 and 66.7% versus 35.6%, P < 0.02, respectively). Among men who reported holding their phones ≤50 cm from the groin, a non-significantly higher rate of abnormal sperm concentration was found (47.1% versus 11.1%). Multivariate analysis revealed that talking while charging the device and smoking were risk factors for abnormal sperm concentration (OR = 4.13 [95% CI 1.28-13.3], P < 0.018 and OR = 3.04 [95% CI 1.14-8.13], P < 0.027, respectively). Our findings suggest that certain aspects of cell phone usage may bear adverse effects on sperm concentration. Investigation using large-scale studies is thus needed.

Concepts: Electromagnetic radiation, Electromagnetic spectrum, Semen analysis, Semen, Mobile phone, Radio, Fertility medicine, Semen quality


This study aimed to determine whether follicular output rate (FORT) can predict the clinical pregnancy rate in women with unexplained infertility undergoing IVF/ICSI. This was a prospective study conducted at Dar El Teb subfertility centre in Cairo between June 2014 and July 2016. A total of 303 women with unexplained infertility, who were undergoing IVF/ICSI, were divided into three groups according to FORT tertile values. FORT was calculated as pre-ovulatory follicle count/antral follicle count × 100. There was a progressive and significant increase from the low to the high FORT groups in the clinical pregnancy rate (29.9%, 43.3% and 57.8%; P < 0.001), number of retrieved oocytes (5.4 ± 1.5, versus 6.8 ± 2.8, and 7.4 ± 2.1; P < 0.001), and fertilization rate (48.4 ± 21.8 versus 55.3 ± 20.3 and 57.4 ± 19.2; P = 0.006). Multivariate logistic regression analysis revealed that the correlation between FORT and pregnancy was independent of potential confounding factors (P = 0.008). We concluded that FORT is an independent variable affecting the clinical pregnancy rate in IVF/ICSI cycles. Higher FORT values had better oocyte yield and clinical pregnancy rates in women with unexplained infertility undergoing IVF/ICSI with potentially normal ovarian response.

Concepts: Regression analysis, Cohort study, Logistic regression, Pregnancy, Experimental design, Clinical trial, In vitro fertilisation, Pregnancy rate


Human pre-ovulatory follicular fluid (FF) contains a higher concentration of melatonin than serum. The aim of this study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcomes of an in-vitro maturation (IVM) IVF-embryo transfer programme for patients with polycystic ovarian syndrome (PCOS). Melatonin concentrations in the culture media of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the clinical outcomes after using IVM media with or without melatonin were analysed. In the culture media of GC or COC, melatonin concentrations gradually increased. When human chorionic gonadotrophin priming protocols were used, implantation rates in the melatonin-supplemented group were higher than those of the non-supplemented control group (P<0.05). Pregnancy rates were also higher, although not significantly. The findings suggest that the addition of melatonin to IVM media may improve the cytoplasmic maturation of human immature oocytes and subsequent clinical outcomes. It is speculated that follicular melatonin may be released from luteinizing GC during late folliculogenesis and that melatonin supplementation may be used to improve the clinical outcomes of IVM IVF-embryo transfer. Melatonin is primarily produced by the pineal gland and regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. Interestingly, human pre-ovulatory follicular fluid contains a higher concentration of melatonin than serum. However, in contrast to animal studies, the direct role of melatonin on oocyte maturation in the human system has not yet been investigated. So, the aim of the study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcome of an in-vitro maturation (IVM) IVF-embryo transfer programme for PCOS patients. The melatonin concentrations in culture medium of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the clinical outcomes of IVM IVF-embryo transfer using IVM medium alone or supplemented with melatonin were analysed. In the culture media of GC or COC, the melatonin concentration gradually increased. With human chorionic gonadotrophin priming, the pregnancy and implantation rates in the melatonin-supplemented group were higher than those of the non-supplemented control (P<0.05). Our findings suggest that follicular melatonin is released from luteinizing GC during late folliculogenesis and plays a positive role in oocyte maturation. Therefore, addition of melatonin into IVM medium may improve cytoplasmic maturation of human immature oocytes and subsequent clinical outcomes.

Concepts: Luteinizing hormone, Pineal gland, Human chorionic gonadotropin, Circadian rhythm, Ovulation, Polycystic ovary syndrome, Folliculogenesis, Melatonin


Incubators in the IVF laboratory play a pivotal role in providing a stable and appropriate culture environment required for optimizing embryo development and clinical outcomes. With technological advances, several types of incubators are now available and careful consideration is required for selection. Examination of variables, such as recovery/stabilization of temperature, gas atmosphere and humidity, as well as understanding various approaches utilized by each device to regulate these variables, is critical. Additionally, a comprehensive examination of clinical studies that compare various incubators may provide insight into their efficacy. Other factors, both technical and practical, must also be considered when selecting an incubator. Importantly, proper management, including patient volume and workflow, is paramount in optimizing function of any incubator, regardless of the technology incorporated. This review highlights incubator function and reviews key environmental variables controlled and the technology utilized in various units. Additionally, existing comparative studies focused on incubator recovery and clinical outcomes are critically analysed. Finally, strategies employed for incubator management, as well as future potential incubator improvements are discussed. While existing reports indicate that smaller benchtop/topload incubators provide faster recovery of environmental variables, there is no clear advantage of any particular incubator based on clinical outcomes. During the IVF procedure, gametes and embryos spend the majority of their time within the confines of the laboratory incubator. Maintaining environmental stability inside the incubator chamber is therefore critical to reduce environmental stressors and to maintain appropriate growth conditions. This makes the laboratory incubator one of the most important pieces of equipment within the IVF laboratory and highlights the importance of incubator selection, which is one of the key decisions within the IVF laboratory. Paramount in the process of making an informed decision regarding IVF incubator selection is knowledge of incubator technology and functioning. Different type of gas sensors, varying methods of temperature regulation and size of the incubator are all-important variables for consideration when selecting from an ever-growing number of incubator options. Furthermore, analysis of existing comparative studies may offer insight into incubator function, although many of the existing studies fail to control for key variables that can impact growth conditions. Importantly, regardless of the incubator or its technology, proper incubator management is critical to optimize embryo development and assisted reproductive outcomes. An appropriate number of incubators and workflow management are essential to help ensure proper growth conditions.

Concepts: Pregnancy, Comparison, Embryo, Avicenna, Mesoderm, Management, Technology, Comprehensive examination


Preimplantation genetic diagnosis of aneuploidy (PGD-A) with comprehensive chromosome analysis has been known to improve pregnancy outcomes. Accuracy in detecting sex chromosomes becomes important when selecting against embryos at risk for sex-linked disorders. A total of 21,356 PGD-A cycles consisting of day-3 (cleavage) or day-5 (blastocyst) biopsies were received at the same laboratory for PGD-A via fluorescence in situ hybridization (FISH) or array comparative genome hybridization (aCGH) from multiple fertility centres. The misdiagnosis rates were 0.12% (Wilson 95% CI 0.05 to 0.25%) in day-3 FISH cycles, 0.48% (Wilson 95% CI 0.19 to 1.22%) in day-3 aCGH cycles and 0.0% (Wilson 95% CI 0 to 0.26) in day-5 aCGH cycles. Although rare, the likely causative biological event for true misdiagnosis is embryonic XX/XY mosaicism. Reanalysis of 1219 abnormal cleavage-stage research embryos revealed a 73% incidence of minor and major mosaicism. Only four (0.3%) embryos were found to be diploid and contained XX and XY cells that could potentially account for the misdiagnosis of sex. Our investigation identified errors leading to misdiagnosis and their attribution to specific events during PGD-A testing. The reported misdiagnosis rates suggest that PGD-A for sex determination is highly accurate, particularly when using aCGH applied to blastocyst biopsies.

Concepts: Gene, Pregnancy, Genetics, Chromosome, Cytogenetics, Preimplantation genetic diagnosis, Metaphase, Comparative genomic hybridization


Our understanding of the composition of the microbial communities that inhabit the human body, known as the ‘microbiome’, is aided by the development of non-culture-dependent DNA sequencing. It is increasingly apparent that the balance of microbial species greatly affects the health of the host. Disturbances in the composition of bacterial communities have been shown to contribute to various disease states, and there is a growing body of evidence that the vaginal microbiota, which is unique to each woman, plays an important role in determining many facets of reproductive health. The purpose of this review is to investigate what is currently known about the composition of the vaginal microbiome, including what is considered ‘normal’ in terms of bacterial species and abundance. We will investigate the impact of vaginal microbiome composition on reproductive outcomes within the context of infertility treatments, and the implications this has been shown to have on assisted reproductive technology procedures.

Concepts: DNA, Archaea, Human, Bacteria, Organism, Chromosome, Human body, Microorganism


The use of donor sperm is increasing, yet limited information is available about the health and development of children conceived from donor sperm. This retrospective descriptive study aimed to assess health and development in a cohort of school-aged children who were conceived using donor sperm. Participants included 224 children, aged 5-11 years, who were conceived using donor sperm. Participants' mothers completed a questionnaire comprising validated scales examining their child’s current and past physical, psychosocial and mental health, healthcare needs and child development, as well as the mothers' health and wellbeing. At the conclusion of the study, the response rate was 296 out of 407 (72.7%), with a participation rate of 224 out o 407 (55.0%). Compared with the normative Australian population, sperm donor-conceived children had similar physical, psychosocial and mental health and development. A modest increase in healthcare needs was evident. The study concludes that in school-aged children conceived using donor sperm, most aspects of child health and wellbeing are similar to the general population.

Concepts: Psychology, Participation, Economics, Child, Childhood, Developmental psychology, Human development, Gross domestic product


In the USA and other countries, oocyte donation is gaining increasing importance. Although sufficient data exist on procedure-associated short-term risks for oocyte donors, such as ovarian hyperstimulation syndrome, long-term follow-up studies of egg donors are lacking and their health risks are unknown. The lack of information may be misleadingly interpreted as lack of risk. Long-term hormone replacement therapy is recognized as a risk factor for breast cancer; the breast cancer risk of ovarian stimulation for egg donors is unknown but is a possibility. This commentary describes five individual cases of egg donors who developed breast cancer (four out of five women in their 30s) despite negative genetic testing results. Additionally, we summarize available studies of breast cancer in infertile women who experienced IVF. We emphasize the need to create egg donor registries that will facilitate long-term studies on egg donors. Until this information is available, we call for more realistic explanations to egg donors about the lack of knowledge of long-term risks as well as more transparent informed consent documents.

Concepts: Pregnancy, Cancer, Estrogen, Pleural effusion, In vitro fertilisation, Assisted reproductive technology, Anovulation, Fertility medicine