Mitochondrial DNA (mtDNA) encodes key proteins associated with the process of oxidative phosphorylation. Defects to mtDNA cause severe disease phenotypes that can affect offspring survival. The aim of this review is to identify how mtDNA is replicated as it transits from the fertilized oocyte into the preimplantation embryo, the fetus and offspring. Approaches for deriving offspring and embryonic stem cells (ESCs) are analysed to determine their potential application for the prevention and treatment of mtDNA disease.
METHODS
The scientific literature was investigated to determine how mtDNA is transmitted, replicated and segregated during pluripotency, differentiation and development. It was also probed to understand how the mtDNA nucleoid is regulated in somatic cells.
RESULTS
mtDNA replication is strictly down-regulated from the fertilized oocyte through the preimplantation embryo. At the blastocyst stage, the onset of mtDNA replication is specific to the trophectodermal cells. The inner cell mass cells restrict mtDNA replication until they receive the key signals to commit to specific cell types. However, it is necessary to determine whether somatic cells reprogrammed through somatic cell nuclear transfer, induced pluripotency or fusion to an ESC are able to regulate mtDNA replication so that they can be used for patient-specific cell therapies and to model disease.
CONCLUSIONS
Prevention of the transmission of mtDNA disease from one generation to the next is still restricted by our lack of understanding as to how to ensure that a donor karyoplast transferred to an enucleated oocyte is free of accompanying mutant mtDNA. Techniques still need to be developed if stem cells are to be used to treat mtDNA disease in those patients already suffering from the phenotype.
Patient-centered reproductive medicine (PCRM) is important for quality of care, and this is increasingly being recognized. However, its scientific basis is unclear. The main research questions addressed in this review are: ‘How has the patients' perspective on fertility care been examined (method and quality)?’ and ‘What is the perspective of patients in developed countries on fertility care?’.
METHODS
A systematic search of electronic databases was conducted and inclusion criteria with respect to eligibility and quality were applied. The methodology of the studies was critically appraised; the findings of the studies were synthesized and organized according to: patients' value clarification and assessment of service quality and dimensions of patient-centeredness. Additionally data on patient preferences and determinants of patients' perspective on care were collected.
RESULTS
In 51 selected studies, patients' perspective on fertility care was examined with (few or many item) questionnaires and/or qualitative interviews. Significant methodological problems were observed. Fertility patients attached importance to seven out of eight dimensions of patient-centeredness (Picker institute) and two new dimensions ‘fertility clinic staff’ and ‘skills’ were developed. Overall, fertility patients want to be treated like human beings with a need for: medical skills, respect, coordination, accessibility, information, comfort, support, partner involvement and a good attitude of and relationship with fertility clinic staff. Patients' preferences between procedures and demographic, medical and psychological determinants of their perspective were defined.
CONCLUSIONS
Fertility patients have ‘human needs’ besides their need for medical care. Evidence on PCRM is available but significant methodological limitations call for the development and validation of a European questionnaire.
Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances which include impaired insulin signalling and glucose metabolism in ovarian follicles. The oocyte is metabolically dependent upon its follicle environment during development, but it is unclear whether PCOS or polycystic ovarian (PCO) morphology alone affect oocyte metabolism and energy-demanding processes such as meiosis.
METHODS
Immature human oocytes were donated by PCOS (n = 14), PCO (n = 14) and control (n = 46) patients attending the assisted conception programme at Leeds Teaching Hospitals NHS Trust. Oocytes were cultured individually and carbohydrate metabolism was assessed during overnight in vitro maturation (IVM). Meiotic status was assessed and oocyte intracellular nicotinamide adenine dinucleotide phosphate (NAD(P)H) content and mitochondria activity were measured prior to karyotype analysis by multifluor in situ hybridization.
RESULTS
Patient aetiology had no significant effect on oocyte maturation potential or incidence of numerical chromosome abnormalities (44%), although PCOS and PCO oocytes were more likely to suffer predivision. Group G chromosomes were most likely to be involved in non-disjunction and predivision. PCOS was associated with increased glucose consumption (2.06 ± 0.43 and 0.54 ± 0.12 pmol/h for PCOS and control oocytes, respectively) and increased pyruvate consumption (18.4 ± 1.2 and 13.9 ± 0.9 pmol/h for PCOS and control oocytes, respectively) during IVM. Prior prescription of metformin significantly attenuated pyruvate consumption by maturing oocytes (8.5 ± 1.8 pmol/h) from PCOS patients. Oocytes from PCO patients had intermediate metabolism profiles. Higher pyruvate turnover was associated with abnormal oocyte karyotypes (13.4 ± 1.9 and 19.9 ± 2.1 pmol/h for normal versus abnormal oocytes, respectively). Similarly, oocyte NAD(P)H content was 1.35-fold higher in abnormal oocytes.
CONCLUSIONS
The chromosomal constitution of in vitro matured oocytes from PCOS is similar to that of controls, but aspects of oocyte metabolism are perturbed by PCOS. Elevated pyruvate consumption was associated with abnormal oocyte karyotype.
Androgens and the androgen receptor (AR) have well known roles in male reproduction, and recent genetic mouse models inactivating the Ar gene have conclusively defined a role for androgens in female reproduction. In males, AR gene inactivation severely disrupts spermatogenesis by interrupting completion of meiosis, thereby eliminating production of mature sperm leading to male sterility. These effects have overshadowed the study of additional post-meiotic androgen effects required for the production of fully functional spermatozoa, as well as the production of females with complete androgen insensitivity which cannot be produced by natural breeding. However, these limitations have been overcome by the creation of global and cell-specific AR knockout (ARKO) mouse models using Cre–LoxP genetic engineering.
METHODS
Pubmed searches were carried out using the following search terms: androgen receptor, knockout mouse and fertility. Articles published before the end of November 2009 were included.
RESULTS
These experimental models have identified cell-specific AR-mediated androgen actions in testis and androgen actions in sex accessory glands independent of testicular effects which are crucial for sperm maturation, motion and fertilizing ability. The ability to produce homozygous ARKO females has revealed that AR-mediated androgen actions are important for normal female fertility. AR function is required for full functionality in follicle health, development and ovulation through both intra-ovarian and neuroendocrine mechanisms.
CONCLUSIONS
ARKO mouse models provide valuable tools to unravel novel roles of AR-mediated actions in male and female reproductive function, and new insights into the role of androgens in human reproductive function.
The three azoospermia factor (AZF) regions of the Y chromosome represent genomic niches for spermatogenesis genes. Yet, the most distal region, AZFc, is a major generator of large-scale variation in the human genome. Determining to what extent this variability affects spermatogenesis is a highly contentious topic in human reproduction.
METHODS
In this review, an extensive characterization of the molecular mechanisms responsible for AZFc genotypical variation is undertaken. Such data are complemented with the assessment of the clinical consequences for male fertility imputable to the different AZFc variants. For this, a critical re-evaluation of 23 association studies was performed in order to extract unifying conclusions by curtailing methodological heterogeneities.
RESULTS
Intrachromosomal homologous recombination mechanisms, either crossover or non-crossover based, are the main drivers for AZFc genetic diversity. In particular, rearrangements affecting gene dosage are the most likely to introduce phenotypical disruptions in the spermatogenic profile. In the specific cases of partial AZFc deletions, both the actual existence and the severity of the spermatogenic defect are dependent on the evolutionary background of the Y chromosome.
CONCLUSIONS
AZFc is one of the most genetically dynamic regions in the human genome. This property may serve as counter against the genetic degeneracy associated with the lack of a meiotic partner. However, such strategy comes at a price: some rearrangements represent a risk factor or a de-facto causative agent of spermatogenic disruption. Interestingly, this precarious balance is modulated, among other yet unknown factors, by the evolutionary history of the Y chromosome.
Pre-eclampsia is a syndrome of heterogeneous origin characterized by deficient placentation due to the inability of the cytotrophoblast to acquire an invasive phenotype and to remodel the uterine spiral arteries. One of the main problems observed early in pre-eclampsia is an altered regulation of the immune system, where the shift toward a Th2 cytokine profile observed in normal pregnancies, does not occur. In pre-eclampsia, high interferon (IFN)- concentrations are present, along with transforming growth factor-β cytokines, which retard migration of cytotrophoblasts.
METHODS
A review of the scientific literature was performed on the immunological factors associated with the origins of pre-eclampsia. The various components of the immune system that may be participating in the aberrant immune activation that pathologically affect early pregnancy events and inhibit cytotrophoblast invasion were identified.
RESULTS AND CONCLUSIONS
Cells and their signaling and regulatory molecules have been implicated in the immunological alterations found in the placental microenvironment of patients who develop pre-eclampsia. One of the main differences found in pre-eclampsia is a shift toward Th1 responses and the production of IFN-. The origin of IFN- is not clearly identified and could be the uterine natural killer cells, the placental dendritic cells modulating Th responses, alterations in synthesis of or response to regulatory molecules, or changes in the function of regulatory T cells in pregnancy. Aberrant immune responses promoting pre-eclampsia may also be due to an altered fetal allorecognition or to inflammatory triggers. Understanding the immunological basis for pre-eclampsia will expand knowledge regarding other adverse pregnancy outcomes.
We assessed sperm DNA fragmentation index (DFI) in cancer patients before and after treatment to evaluate if sperm DNA integrity is compromised by cancer itself or its treatment.
METHODS
In a prospective study, DFI was assessed in 127 patients diagnosed with testicular germ cell tumours (TGCT), Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL) and various malignancies. The severity of cancer and tumour markers at diagnosis was recorded. Follow-up DFI after treatment was available in 52 patients who were mostly less severely affected.
RESULTS
In patients diagnosed with TGCT, HL and various malignancies, pretreatment DFI levels were not significantly different from that of proven fertile controls, but in patients with NHL an increased DFI was found. An overall significant decrease in post-treatment DFI (13.2% range 5.0–70.5) compared with pretreatment values (17.1% range 5.1–66.6) was found (P = 0.040). In TGCT patients, post-treatment DFI was significantly higher in patients who were treated with radiotherapy (16.9% range 11.5–39.9) compared with that in patients treated with chemotherapy (CT) alone (10.9% range 5.5–39.9) (P = 0.037). In HL patients, the type of treatment or number of CT cycles was not associated with DFI. Overall, post-treatment DFI in cancer patients was not significantly different from that of proven fertile controls.
CONCLUSIONS
In this study, the presence of cancer does not seem to negatively affect the sperm DNA integrity in TGCT and HL patients; only NHL patients showed increased DFI at the time of diagnosis compared with healthy controls. Our results confirm previous reports that DFI decreases significantly following various anti-cancer treatments. In contrast, radiotherapy in TGCT patients is associated with an increase in DFI compared with CT treatment alone.
Since 1999, we have treated HIV-positive men with sperm washing as part of a risk-reduction programme.
METHODS
Retrospective analysis of the sperm-washing database from the treatment of 245 couples with 439 cycles of intrauterine insemination assessed the effects of patient factors (age, maternal FSH, rank of attempt), markers of HIV-disease [time since diagnosis, CD4 count, viral load (VL), use of highly active antiretroviral therapy (HAART)], cycle factors (natural versus stimulated, number of follicles, fresh versus frozen sperm) and sperm parameters on clinical (CPR) and ongoing pregnancy rate (OPR).
RESULTS
Overall 111–245 (45.4%) couples achieved a clinical pregnancy (CPR: 13.5% and OPR: 9.6% per insemination) with no seroconversions. The mean duration since HIV diagnosis was 5.8 years, 73% of men were on antiretroviral therapy, there was an undetectable VL in 64% and the median CD4 was 409 cells/mm3. A significantly decreased OPR and a non-significantly increased miscarriage rate (MR) was observed after the female age of 40. Similarly, there was a significant increased OPR and decreased MR for women with a mean cycle maternal FSH of <6.4 IU/l. There was no effect of VL, CD4 count, use of HAART or time since diagnosis on the outcome. Nor was there a difference in the OPR according to paternal age, rank of attempt, cycle regime or number of follicles. Semen volume, sperm concentration, total count and progressive motility and post-wash concentration, progressive motility and total motile count inseminated were significantly higher in successful cycles. The use of frozen sperm had a significant negative impact on outcome.
CONCLUSIONS
This study of the potential safe and successful reproductive options available to HIV-positive men demonstrates that maternal age and semen quality, rather than HIV factors, remain the most important determinants of cycle success.
In this 10th European IVF-monitoring (EIM) report, the results of assisted reproductive techniques from treatments initiated in Europe during 2006 are presented. Data were mainly collected from existing national registers.
METHODS
From 32 countries, 998 clinics reported 458 759 treatment cycles including: IVF (117 318), ICSI (232 844), frozen embryo replacement (FER, 86 059), egg donation (ED, 12 685), preimplantation genetic diagnosis/screening (6561), in vitro maturation (247) and frozen oocytes replacements (3498). Overall this represents a 9.7% increase in activity since 2005, which is partly due to an increase in registers (seven more countries with complete coverage). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 22 countries. A total of 134 261 IUI-H and 24 339 IUI-D cycles were included.
RESULTS
In 20 countries, where all clinics reported to the IVF register, a total of 359 110 assisted reproductive technology (ART) cycles were performed in a population of 422.5 million, corresponding to 850 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 29.0 and 32.4%, respectively. For ICSI, the corresponding rates were 29.9 and 33.0%. After IUI-H the delivery rate was 9.2% in women below 40. After IVF and ICSI the distribution of transfer of one, two, three and four or more embryos was 22.1, 57.3, 19.0 and 1.6%, respectively. Compared with 2005, fewer embryos were replaced per transfer, but significant national differences in practice were apparent. The proportion of singleton, twin and triplet deliveries after IVF and ICSI combined was 79.2, 19.9 and 0.9%, respectively. This gives a total multiple delivery rates of 20.8% compared with 21.8% in 2005 and 22.7% in 2004. IUI-H in women below 40 years of age resulted in 10.6% twin and 0.6% triplet pregnancies.
CONCLUSIONS
Compared with previous years, the reported number of ART cycles in Europe has increased, pregnancy rates have increased marginally, even though fewer embryos were transferred and the multiple delivery rates have declined.
Our objective was to determine what effect maternal BMI has on fetal growth rate in the early first trimester.
METHODS
This was a prospective observational study of singleton pregnancies with certain dates, initially presenting for a transvaginal scan (TVS) before 12 weeks of gestation. Maternal characteristics (BMI, ethnicity, maternal age, obstetric history, abdominal pain and vaginal bleeding) were recorded. Fetal crown-rump length (CRL) was measured at the initial scan, and at subsequent ultrasound assessments. In order to assess the fetal growth rates, women with at least two CRL measurements were included in the analysis. A mixed-linear effects model analysis was performed to determine whether BMI influences the rate of change in CRL.
RESULTS
A total of 264 pregnancies were analysed. The median BMI was 23.55 (range 16–45), median age was 32 (17–44) and the proportion of white, black and Asian women was 61.0, 15.5 and 5.3%, respectively. Mean gestational age (GA) at first TVS was 56 (range 33–84) days. Studying CRL as a function of GA with a mixed-linear effects model showed that this relationship was neither significantly influenced by BMI when modelling BMI as a continuous variable (P = 0.7529), nor when modelling it as a categorical variable using the WHO criteria (P = 0.8904).
CONCLUSIONS
Dating by CRL influences subsequent growth assessment and previous studies have suggested that first trimester fetal growth rates may be influenced by ethnicity and age. Our data however suggest that maternal BMI does not significantly influence early fetal growth.
Oocytes in humans, mice and other mammals lack identifiable centrioles. The proximal centriole brought in by the fertilizing sperm in humans and most other mammals appears to gives rise to the centrioles at the spindle poles in the zygote, and is believed to indicate that centrioles are inherited through the paternal lineage. However, both the proximal and distal sperm centrioles degenerate in mice and other rodents. A bipolar mitotic spindle nucleates from multiple centrosome-like structures in the mouse zygote and centrioles are not seen until the blastocyst stage, suggesting that centrioles are inherited through the maternal lineage in mice. We previously identified speriolin as a spermatogenic cell-specific binding partner of Cdc20 that co-localizes with pericentrin in mouse spermatocytes and is present in the centrosome in round spermatids.
METHODS
The nature and localization of speriolin in mouse and human sperm and the fate of speriolin following fertilization in the mouse were determined using immunofluorescence microscopy, immunoelectron microscopy and western blotting.
RESULTS
Speriolin surrounds the intact proximal centriole in human sperm, but is localized at the periphery of the disordered distal centriole in mouse sperm. Human speriolin contains an internal 163-amino acid region not present in mouse that may contribute to localization differences. Speriolin is carried into the mouse oocyte during fertilization and remains associated with the decondensing sperm head in zygotes. The speriolin spot appears to undergo duplication or splitting during the first interphase and is detectable in 2-cell embryos.
CONCLUSIONS
Speriolin is a novel centrosomal protein present in the connecting piece region of mouse and human sperm that is transmitted to the mouse zygote and can be detected throughout the first mitotic division.
Post-zygotic chromosome segregation errors are very common in human embryos after in vitro fertilization, resulting in mosaic embryos. However, the significance of mosaicism for the developmental potential of early embryos is unknown. We assessed chromosomal constitution and development of embryos from compaction to the peri-implantation stage.
METHODS
From 112 cryopreserved Day 4 human embryos donated for research, 21 were immediately fixed and all cells were analysed by fluorescent in situ hybridization (FISH) for chromosomes 1, 7, 13, 15, 16, 18, 21, 22, X and Y. The remaining 91 embryos were thawed, with 54 embryos undergoing biopsy of one or two cells which were fixed and analysed by FISH. Biopsied embryos were kept in standard culture conditions for 24 h. Embryos arrested before cavitation (n = 24) were fixed whereas developing Day 5 blastocysts (n = 24) were co-cultured for a further 72 h on an endometrial monolayer followed by fixation. Cell numbers were counted and all nuclei were analysed by FISH. Data from a previous FISH analysis on cryopreserved good-quality Day 5 blastocysts (n = 36) were also included in the present study.
RESULTS
FISH analysis was successful for 18 Day 4 fixed embryos and, according to our definition, 83% were mosaic and 11% showed a chaotic chromosomal constitution. FISH analysis of two blastomeres from Day 4 developing embryos showed that 54% were mosaic, 40% were normal and 6% were abnormal. Analysis of Day 4, 5 and 8 whole embryos showed a decrease in incidence of mosaicism over time, from 83% on Day 4 to 42% on Day 8. A significant positive correlation was observed between the total cell number and the percentage of normal cells in developing Day 5 and Day 8 embryos but not in developing Day 4 or embryos arrested before cavitation.
CONCLUSIONS
These data suggest that both the developmental arrest of a significant proportion of mosaic embryos on Day 4, and the cell death or reduced proliferation of aneuploid cells within an embryo may be responsible for the observed decrease of aneuploid blastomeres from compaction to the peri-implantation stage.
There are conflicting results on whether the rate of blastocyst development before freezing influences the outcome of frozen-thawed blastocyst transfers.
METHODS
We conducted a systematic review and meta-analysis of controlled studies to compare pregnancy outcomes following transfer of thawed blastocysts that were frozen either on Day 5 or Day 6 following fertilization in vitro. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science. Study selection and data extraction were conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment.
RESULTS
We identified 15 controlled studies comprising 2502 frozen-thawed transfers involving blastocysts that were either frozen on Day 5 or Day 6. Meta-analysis of these studies showed significantly higher clinical pregnancy rate [relative risk (RR) = 1.14, 95% confidence interval (CI): 1.03–1.26, P = 0.01] and ongoing pregnancy/live birth rate (RR = 1.15, 95% CI: 1.01–1.30, P = 0.03) with Day 5 compared with Day 6 frozen-thawed blastocyst transfers. Sensitivity analysis of those studies where blastocysts frozen on Day 5 or Day 6 were at the same stage of development showed no significant difference in the clinical pregnancy rate (RR = 1.07, 95% CI: 0.87–1.33, P = 0.51) and ongoing pregnancy/live birth rate (RR = 1.08, 95% CI: 0.92–1.27, P = 0.36).
CONCLUSION
Slower developing blastocysts cryopreserved on Day 6 but at the same stage of development as those developing to the blastocyst stage on Day 5 have similar clinical pregnancy and ongoing pregnancy/live birth rates following frozen-thawed blastocyst transfers.
Recurrent fetal loss (RFL) is a prevalent problem affecting ~1% of all women of childbearing age. Many factors can lead to RFL; however, recent studies have indicated the important role of the maternal immune system in this process. The human leukocyte antigens (HLA), HLA-linked genes and regulatory factors play an important role in fetal loss and in fetal development. The current retrospective study was preformed to examine the HLA alleles shared between couples with RFL in Saudi Arabia, using a large cohort of women (having three or more RFL). Specific HLA alleles that could influence this condition, or the number of miscarriages experienced, were expected to be highlighted in this way.
METHODS
A total of 253 consecutive patients who visited the RFL clinic at the King AbdulAziz Medical City, National Guard Hospital in Riyadh were included in this study. They included 54 consanguineous couples, 132 non-consanguineous couples and another 67 couples shared only their tribal origin. Clinical examinations as well as laboratory investigations were carried out on each patient. Class I HLA, HLA-A, HLA-B and HLA-C, and Class II HLA, HLA-DR and HLA-DQ, were typed for each patient and their partner.
RESULTS
No relationship was seen between sharing of HLA alleles and the number of RFL experienced by the couples, among neither consanguineous nor non-consanguineous couples.
CONCLUSIONS
Although the results of this study suggest that HLA sharing is not an indicative factor in RFL, definitive conclusions on this topic must be based on large case–control studies.
The debate continues between advocates of the shaving technique and supporters of bowel resection in case of deep endometriosis with rectal muscularis involvement, despite little evidence for better improvement with bowel resection.
METHODS
We analyzed complication, pregnancy and recurrence rates after deep endometriotic nodule excision by shaving surgery. This is a prospective analysis of 500 cases (<40 years old) of deep endometriotic nodules.
RESULTS
Laparoscopic nodule resection was performed successfully in all cases. Major complications included: (i) rectal perforation in seven cases (1.4%); (ii) ureteral injury in four cases (0.8%); (iii) blood loss >300 ml in one case (0.2%); and (iv) urinary retention in four cases (0.8%). The median follow-up duration was 3.1 years (range 2–6 years). In our prospective series of 500 women, 388 wished to conceive. Of this number, 221 (57%) became pregnant naturally and 107 by means of IVF. In total, 328 women (84%) conceived. The recurrence rate was 8% among these 500 women, and it was significantly lower (P < 0.05) in women who became pregnant (3.6%) than in those who did not (15%). In women who failed to conceive, or were not interested in conceiving, severe pelvic pain recurred in 16–20% of patients.
CONCLUSION
In young women, conservative surgery using the shaving technique preserves organs, nerves and the vascular blood supply, yielding a high pregnancy rate and low complication and recurrence rates. There is a need, however, for further strong and energetic debate to weigh up the benefits of shaving (debulking surgery) versus rectal resection (radical surgery).
The aim of the present study was to evaluate the efficacy of misoprostol administered orally, vaginally, or sublingually on cervical ripening before hysteroscopic surgery in premenopausal non-pregnant women.
METHODS
Non-pregnant premenopausal women scheduled for operative hysteroscopy (with a 10-mm hysteroscope) were assigned by computerized randomization to receive 400 mg of misoprostol, administered either orally or vaginally 6–8 h prior to surgery or 400 mg sublingually 2–4 h prior to surgery. The primary outcome in this study was the preoperative cervical width as measured by the largest number of Hegar dilators. The time to Hegar number 10 was also recorded along with side effects related to misoprostol and complications during surgery for each group.
RESULTS
Patients were randomized to receive sublingual (n = 47), oral (n = 47) or vaginal (n = 47) misoprostol. The three groups were comparable in terms of age, BMI (body mass index), parity, gravidity, history of vaginal delivery, post-operative pathological findings and surgeon type. The preoperative cervical width [sublingual: 7.5 ± 2.0 mm (8, 3–10); oral: 7.5 ± 1.9 mm (7, 4–10); vaginal: 7.6 ± 2.4 mm (8, 1–10)] was statistically similar among the groups. The time to Hegar number 10, side effects and complications during the hysteroscopy were comparable among the three groups.
CONCLUSION
A limitation of this study was that the surgeons, but not the patients, were blinded to the test procedures. Nevertheless we found that sublingual, oral and vaginal misoprostol were equally effective for cervical priming before hysteroscopic surgery in premenopausal non-pregnant women.
The trial was registered under ClinicalTrials.gov identifier NCT01024270.
Parthenogenetic embryonic stem cells (PESCs) may have future utilities in cell replacement therapies since they are closely related to the female from which the activated oocyte was obtained. Furthermore, the avoidance of parthenogenetic development in mammals provides the most compelling rationale for the evolution of genomic imprinting, and the biological process of parthenogenesis raises complex issues regarding differential gene expression.
METHODS AND RESULTS
We describe here homozygous rhesus monkey PESCs derived from a spontaneously duplicated, haploid oocyte genome. Since the effect of homozygosity on PESCs pluripotency and differentiation potential is unknown, we assessed the similarities and differences in pluripotency markers and developmental potential by in vitro and in vivo differentiation of homozygous and heterozygous PESCs. To understand the differences in gene expression regulation between parthenogenetic and biparental embryonic stem cells (ESCs), we conducted microarray analysis of genome-wide mRNA profiles of primate PESCs and ESCs derived from fertilized embryos using the Affymetrix Rhesus Macaque Genome array. Several known paternally imprinted genes were in the highly down-regulated group in PESCs compared with ESCs. Furthermore, allele-specific expression analysis of other genes whose expression is also down-regulated in PESCs, led to the identification of one novel imprinted gene, inositol polyphosphate-5-phosphatase F (INPP5F), which was exclusively expressed from a paternal allele.
CONCLUSION
Our findings suggest that PESCs could be used as a model for studying genomic imprinting, and in the discovery of novel imprinted genes.
Worldwide there is an increasing number of families created by oocyte donation (OD). The aim of this study was to gather information about parents' plans of disclosure to their child and to other people, as well as parents' attitudes and level of satisfaction up to 15 years after their OD treatment.
METHODS
A questionnaire with separate material for each partner was sent to all parents (167 mothers, 163 fathers) who had had a child after treatment with donated oocytes at Väestöliitto Fertility Clinics in Helsinki during 1992–2006. These parents had a total of 231 children aged 1–14 years. Parents were asked if they had told or intended to tell their child about his/her origin and how and when they had done so and about the reasons to disclose or not. Other questions were about openness towards other people, concerns about donor characteristics, counselling and feelings towards the child.
RESULTS
Of the mothers, 61.1%, and of the fathers, 60.0%, had told or intended to tell the child of his/her conception. Of children over 3 years of age, 26% had already been informed. There was a statistically significant difference between parental telling in different age groups of children (P = 0.011, 2). In the youngest age group (1–3 years), 83.3% of parents were inclined to disclosure compared with 44.4% in the oldest age group (13–14 years). A high proportion of mothers (86.7%) and fathers (71.0%) had told other people about the nature of their child's conception. The majority of parents did not have much concern about the characteristics of the donor. A higher proportion of the mothers (24%) compared with fathers (11%) thought that the psychological support had been insufficient. They thought that discussions with health professionals should be arranged routinely after delivery or when it was time to inform the child.
CONCLUSIONS
Parents with young OD children are clearly more inclined to disclosure compared with parents with older children.
High-quality fertility care should be effective and safe, but also patient-centred. However, a suitable instrument for measuring patient-centredness is lacking. This study aims to develop and validate an instrument that can reliably measure patient-centredness in fertility care: patient-centredness questionnaire-infertility (PCQ-infertility).
METHODS
The PCQ's content, addressing 53 care aspects, was generated by seven focus groups with 54 infertile patients. Besides background questions, the questionnaire included one ‘experience item’ and one ‘importance item’ for each care aspect. Thirty Dutch fertility clinics were invited to participate in the validation study. The questionnaire was sent at random to 1200 infertile couples. Psychometric tests included inter-item and reliability analyses. Importance scores were calculated. The discriminative power was determined using multilevel analysis.
RESULTS
The questionnaire was completed by 888 infertile couples (net response 75%) from 29 clinics. The ultimate PCQ-infertility, comprising 46 items and seven subscales, appeared reliable and valid for measuring patient-centredness in fertility care. Of the seven subscales, ‘communication’ received the best ratings and ‘continuity’ the worst. ‘Honesty and clearness on what to expect from fertility care’ appeared most important to patients. Significant differences between clinics were found, even after case-mix adjustment.
CONCLUSION
This study resulted in a valid, reliable and strongly discriminating instrument for measuring patient-centredness in fertility care. The PCQ-infertility can identify shortcomings on patient-centredness and can be adopted for quality improvement. Therefore, fertility care can now be monitored and benchmarked on patient-centredness, as well as on live birth and complication rates.
In order to formulate cost-effective health interventions aimed at preventing infertility it is necessary to identify modifiable risk factors for infertility in sub-Saharan Africa. This case–control study examined potential predictors and their population attributable fraction (PAF%) for various infertility types including lifestyle factors, sexual behaviour and reproductive tract infections (RTIs).
METHODS
Sexually active women aged 21–45 year presenting with infertility problems at the infertility clinic of the Kigali University Teaching Hospital (n = 312), and fertile controls who recently delivered (n = 283) were surveyed together with their male partners. Participants were interviewed about socio-demographic characteristics, sexual behaviours and lifestyle factors, and were tested for HIV and RTIs.
RESULTS
Variables significantly associated with tubal infertility were history of sexual violence [adjusted odds ratio (AOR) 2.41; 95% CI 1.36–4.25]; positive HIV (AOR 2.41; 95% CI 1.36–4.25), herpes simplex virus type 2 (HSV-2; AOR 1.67; 95% CI 1.03–2.71) and Chlamydia trachomatis serology (AOR 1.78; 95% CI 0.99–3.21), and current bacterial vaginosis by Amsel criteria (AOR 1.97; 95% CI 1.12–3.47). Among men, male factor infertility was associated with positive HIV (AOR 2.43; 95% CI 1.31–5.23) and HSV-2 serology (AOR 1.71; 95% CI 1.02–2.87) and current urologic abnormalities (AOR 2.38; 95% CI 1.01–5.31). Positive HSV-2 serostatus carried the greatest PAF% (26%) for tubal infertility, followed by positive HIV serostatus (20%) and history of sexual violence (17%).
CONCLUSIONS
Although temporal relationships are difficult to ascertain, history of sexual violence, HSV-2 infection and HIV infection are important predictors of infertility in Rwanda.
