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1.  Prediction of individual probabilities of livebirth and multiple birth events following in vitro fertilization (IVF): a new outcomes counselling tool for IVF providers and patients using HFEA metrics 
In vitro fertilization (IVF) has become a standard treatment for subfertility after it was demonstrated to be of value to humans in 1978. However, the introduction of IVF into mainstream clinical practice has been accompanied by concerns regarding the number of multiple gestations that it can produce, as multiple births present significant medical consequences to mothers and offspring. When considering IVF as a treatment modality, a balance must be set between the chance of having a live birth and the risk of having a multiple birth. As IVF is often a costly decision for patients—financially, medically, and emotionally—there is benefit from estimating a patient’s specific chance that IVF could result in a birth as fertility treatment options are contemplated. Historically, a patient’s “chance of success” with IVF has been approximated from institution-based statistics, rather than on the basis of any particular clinical parameter (except age). Furthermore, the likelihood of IVF resulting in a twin or triplet outcome must be acknowledged for each patient, given the known increased complications of multiple gestation and consequent increased risk of poor birth outcomes. In this research, we describe a multivariate risk assessment model that incorporates metrics adapted from a national 7.5-year sampling of the Human Fertilisation & Embryology Authority (HFEA) dataset (1991–1998) to predict reproductive outcome (including estimation of multiple birth) after IVF. To our knowledge, is the first Software-as-a-Service (SaaS) application to predict IVF outcome. The approach also includes a confirmation functionality, where clinicians can agree or disagree with the computer-generated outcome predictions. It is anticipated that the emergence of predictive tools will augment the reproductive endocrinology consultation, improve the medical informed consent process by tailoring the outcome assessment to each patient, and reduce the potential for adverse outcomes with IVF.
PMCID: PMC3183499  PMID: 21991292
2.  Folic acid and human reproduction—ten important issues for clinicians 
This article presents data on the current best evidence-based clinical practices and controversies surrounding folic acid supplementation/fortification for the prevention of neural tube defects (NTDs) during early pregnancy. Formatted as a series of ten clinical questions, answers and extensive discussion are provided for each point. We assess the history and evidence behind supplementation and fortification, racial/ethnic disparities in NTDs on a global scale, and present information on risk factors for NTDs other than dietary folic acid deficiency. Also discussed are public health challenges, including disparities in NTD rates, population-wide monitoring of NTDs, and tracking safety data in the post-fortification era. Emerging data are also reviewed regarding the role folic acid may play in malignant processes, cardiovascular disease, male fertility, and other medical conditions.
PMCID: PMC3183498  PMID: 21991291
3.  Male subfertility and the role of micronutrient supplementation: clinical and economic issues 
The concept of male subfertility has evolved rapidly since 2000. This term is discussed based upon evidence relating to its first entrance into the literature, along with contemporary references to its purported incidence and prevalence. Factors affecting sperm quality are described in detail, and available data pertaining to the effects of micronutrients on spermatic parameters and resulting pregnancies are described. The first cost-efficiency analysis of the use of micronutrients vs. assisted reproductive technologies is presented. This paper also describes a therapeutic approach to males, recognizing that many potential fathers have no recourse to medical facilities to evaluate their fertility. At a time when medical dollars are either nonexistent or precious, such an approach using micronutrient supplementation may be cost-effective in developing and possibly even in developed countries.
PMCID: PMC3183500  PMID: 21991290
4.  A population based economic analysis of cross-border payments for fertility services in Luxembourg 
How fertility patients utilise assisted reproductive services can depend on how easy it is to access such services locally. Little data exist to document the extent of economic outflow that accompanies cross-border patient travel specifically for medical procedures that cannot be obtained in country.
In this investigation, data from Luxembourg’s social security agency were used to audit medical reimbursement payments for IVF within and outside the Grand Duchy of Luxembourg between 1998 and 2007. This study interval offered an opportunity to track IVF expenditures before and after IVF was made freely available within the Grand Duchy.
Reimbursement authorizations to IVF providers outside Luxembourg remained stable or slightly elevated until 2005, two years after Luxembourg opened its first IVF centre. Once established in Luxembourg, annual utilisation of the domestic IVF service generally trended upwards (217 cycles in 2003 vs. 569 in 2008). Meanwhile, payments to foreign IVF clinics declined steadily after 2005 reflecting a diminishing number of Luxembourg patients seeking cross-border IVF treatment.
These data represent the most comprehensive register of cross-border reproductive visits in Europe. Since Luxembourg fully reimburses its citizens for health-related expenses irrespective of where the medical service is obtained, the current investigation renders the “out of pocket” effect of IVF fees irrelevant and characterise consumption of elective medical treatments as a function of service site. Further studies are needed to determine if these findings will generalise to other geographic regions.
PMCID: PMC2951751  PMID: 20941372
5.  Comparison of selected cryoprotective agents to stabilize meiotic spindles of human oocytes during cooling 
This study examined the primary effect of selected cryoprotective agents (CPAs) on the meiotic spindles of human oocytes during cooling.
Fresh metaphase II oocytes (n=26) donated from patients undergoing IVF treatment were analyzed via Polscope. In experiment one, 16 oocytes with visible spindle at 37°C were cooled to 20°C and rewarmed to 37°C to test the spindle response to cooling. They were then cooled to 20°C, 10°C, 0°C and rewarmed to 37°C after having been equilibrated with 1.5 M 1,2-propanediol (PROH), 1.5 M dimethyl sulfoxide (DMSO), 1.5 M ethylene glycol (EG) or 10 μM taxol at 37°C. In experiment two, 10 oocytes without visible spindles at 37°C were cooled to 20°C and then equilibrated with PROH, EG and taxol at 20°C. Spindle images were recorded at each temperature.
Meiotic spindles remained visible or became more distinct during cooling to 20°C, 10°C and 0°C when equilibrated with PROH, EG, DMSO and Taxol. Without these agents, meiotic spindles of the same oocytes disappeared after cooling to 20°C.
The primary effect of PROH, EG and DMSO on the meiotic spindle is to stabilize and protect it against low temperature disassembly. A higher equilibration temperature (≥33°C) for oocyte freezing is recommended.
PMCID: PMC2951752  PMID: 20941373
cryoprotective agents; spindle; cryopreservation; human oocyte; cooling; Taxol
6.  Hyaluronan binding assay (HBA) vs. sperm penetration assay (SPA): Can HBA replace the SPA test in male partner screening before in vitro fertilization? 
To determine if a less expensive, easier, and faster to perform HBA test is clinically equal to the more complicated, technically challenging and expensive SPA test as a reliable indicator of sperm fertilizing capacity.
Prospective study.
Andrology laboratory within In Vitro Fertilization Program.
Semen samples from 26 infertility couples were analyzed. Both, normal and male factor patients were included.
Male partner screening with the HBA and the SPA tests.
Main Outcome Measure(s):
Relationship between HBA and SPA test results.
The data obtained in this study showed no statistically significant relationship between the HBA and SPA results. The mean HBA scores 76.3%, 61.3% and 76.8% were statistically not significantly different as compared to patients with negative (<5), grey zone (5–8) and for positive (>8) sperm capacitation index values.
The HBA is not predictive of the results of the SPA. Therefore, HBA test does not reduce the need for and cannot replace the SPA test in male partner screening prior to infertility treatment.
PMCID: PMC2868308  PMID: 20485584
Hyaluronan-binding assay; sperm penetration assay; male partner screening
8.  Comprehensive assessment of serum estradiol impact on selected physiologic markers observed during in-vitro fertilization and embryo transfer cycles 
This investigation assessed the effect of serum estradiol levels on outcomes of in-vitro fertilization and embryo transfer (IVF) cycles.
Materials and method:
This was a retrospective cohort study of 1123 IVF cycles comparing impact of estradiol (E2) levels on follicular development, fertilization, embryo quality, implantation, pregnancy rate, miscarriage rate, and selected obstetric complications.
We found high serum E2 levels to be significantly associated with increased number of mature follicles and mature oocytes retrieved (p<0.01, for both). E2 levels were also associated with more viable and good-quality embryos (p<0.01). There was no significant impact of E2 on oocyte maturation, fertilization rate, embryo quality, or overall pregnancy rates. Moreover, high E2 levels were significantly associated with higher implantation rates and reduced incidence of miscarriage (p<0.05, for both).
Within the safety range in clinical practice, our data demonstrate a generally positive effect of high serum E2 on selected IVF parameters.
PMCID: PMC2868301  PMID: 20485580
Estradiol; in-vitro fertilization; embryo transfer
9.  Perinatal outcomes following transfer of human blastocysts vitrified at day 5, 6 and 7 
Little information is available on perinatal outcome of cryopreserved day-7 blastocyst transfer. In the present report, perinatal outcomes for transfers of cryopreserved blastocysts by a vitrification method were examined with respect to the day of blastocyst expansion among on day 5, 6 or 7 before cryopreservation. We investigated 263 cycles of vitrified-warmed blastocyst stage embryo transfer performed between April 2005 and April 2009, which were reviewed retrospectively. There were 144 cycles with day-5 blastocyst, 100 cycles with day-6 blastocyst, and 19 cycles with day-7 blastocyst transfers. There were no differences among the vitrified day-5, day-6 and day-7 blastocyst transfer groups regarding mean number of embryos transferred, pregnancy rate, implantation rate and miscarriage rate. At this time, 71 deliveries have occurred with no reported abnormalities. There were 47 infants from 41 deliveries with day-5 blastocyst, 26 infants from 23 deliveries with day-6 blastocyst, and 8 infants from 7 deliveries with day-7 blastocyst. There were no differences among the three groups in the mean gestational age, preterm delivery rate and mean birth weight. These results indicated that blastocysts have similar inherent viability regardless of whether they develop by day 5, 6 or 7.
PMCID: PMC2868303  PMID: 20485579
10.  Screening for Y-chromosome microdeletions in a population of infertile males in the Gaza Strip 
Infertility is an extraordinary public health problem in the Arab world, as it affects about 15% of couples seeking children. The male partner is responsible for infertility in approximately half of these cases. Classic microdeletions of the Y-chromosome involving the azoospermia factor (AZF) regions are known to be associated with spermatogenic impairment, and non-obstructive azoospermia must be differentiated on the basis of endocrine evaluation and testicular biopsy. Partial AZFc deletions remain controversial because there is no clear agreement regarding their role in spermatogenic failure. In the current study, 50 fertile males (controls) and 125 patients with primary idiopathic male infertility were studied in order to describe the frequency of Y-chromosome mirodeletions among male infertility patients in the Gaza Strip-Palestine area. No Y chromosome classical microdeletions could be detected in any of the 125 infertile men, suggesting that ethnic factors, genetic background, and Y chromosome haplogroups are key factors in such deletions. On the other hand, six gr/gr and one b1/b3 AZFc partial deletions were detected in the infertile population. The gr/gr deletion was also noted in relatives of four of the six patients with this deletion, and in one of the fertile controls. In conclusion, our study shows that the incidence of Y-chromosome microdeletions in our population is rare; these data suggest that other genetic, epigenetic, nutritional and/or local factors are responsible for impairments in semen parameters observed in this Gazan population. We further hypothesise that the gr/gr deletion is not associated with male infertility, at least in this sub-group.
PMCID: PMC2868306  PMID: 20485582
Idiopathic male infertility; A/oligozoospermia; Y-chromosome microdeletions; AZFc partial deletion
11.  Luteal phase bleeding after IVF cycles: comparison between progesterone vaginal gel and intramuscular progesterone and correlation with pregnancy outcomes 
To compare luteal phase bleeding and pregnancy outcomes in normogonadotropic patients receiving progesterone vaginal gel (PVG) or intramuscular progesterone (IMP) injections.
In this retrospective cohort study, data from 270 patients (292 cycles) undergoing day-3 fresh embryo transfer were analyzed. PVG, 90 mg daily (170 cycles) or IMP, 50 mg daily (122 cycles) began at egg retrieval.
Luteal phase bleeding was significantly more common in the PVG than the IMP group. No significant differences were observed in biochemical pregnancy or spontaneous abortion rates between the two groups. Patients who bled before the pregnancy test had significantly lower total and clinical pregnancy rates than non-bleeders. Total and ongoing pregnancy/delivery rates were higher in the PVG than IMP group, but did not achieve statistical significance.
Luteal phase bleeding was more common in the PVG group than the IMP group, but pregnancy was successful in more patients in the PVG group. Luteal phase bleeding is prevented or delayed during IMP treatment, but patients who bled before the pregnancy test, whether using the gel or injected progesterone, had significantly reduced pregnancy rates compared with non-bleeders.
PMCID: PMC2868307  PMID: 20485581
Assisted reproductive technology; Progesterone; Luteal phase support; Progesterone vaginal gel
12.  Ovarian Hyperstimulation Syndrome: Current Views on Pathophysiology, Risk Factors, Prevention, and Management 
To summarize current views on the pathophysiology, risk factors, prevention, clinical features, and management of Ovarian Hyperstimulation Syndrome (OHSS).
Literature review
OHSS is a condition characterized by increased capillary permeability, and experimental evidence has identified a provocative link to pathologic vasoactive cytokine actions. Although the ultimate physiologic mechanism of OHSS is not yet known, there are well-known risk factors that must be considered during the administration of medications to treat infertility. Clinical features are consequences of third-spaced intravascular fluid, and OHSS may become life-threatening secondary to thromboembolism or compromised pulmonary or cardiovascular function. Cornerstones of prevention have historically included cycle cancellation, coasting, decreased dosing of human chorionic gonadotropin (hCG) trigger, use of an agonist trigger, and cryopreservation of all embryos. Newer methods of prevention include the administration of a dopamine agonist medication. Management options for OHSS include outpatient transvaginal paracentesis, outpatient transabdominal paracentesis, and inpatient hospitalization with or without paracentesis.
OHSS continues to be a serious complication of assisted reproductive therapy (ART), with no universally agreed upon best method of prevention. Coasting and cryopreservation of all embryos are the most commonly used approaches in the literature, but cycle cancellation is the only method that can completely prevent the development of OHSS. Dopamine agonists are currently being investigated to both prevent and improve the clinical course in OHSS. Recent publications suggest that outpatient paracentesis both prevents the need for inpatient hospitalization and is a cost-effective strategy.
PMCID: PMC2868304  PMID: 20485578
ovarian hyperstimulation syndrome; ascites; coasting; embryo cryopreservation; paracentesis
13.  Hyperfertility, obesity, and stillbirth: new considerations for clinical practice 
This research focuses on two well known phenomenon that regularly confront obstetricians on a worldwide basis. The first is hyperfertility, whose effects are well known within and outside the obstetrics community. The second is obesity, a problem of growing importance throughout the developed and developing world. Each is discussed in view of recently published evidence. In this work, we show how these two concepts interlock and how they represent a substantial clinical challenge to all physicians providing care to reproductive aged women.
PMCID: PMC2868305  PMID: 20485577
15.  Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status, neural tube defects, schizophrenia, and vasculopathy 
Several conditions apparent at birth, e.g., neural tube defects (NTDs) and cardiac anomalies, are associated with polymorphisms in folate-related genes, such as the 677C → T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Similar associations have been established for several constitutional chronic diseases in adulthood, such as schizophrenia, cardiovascular diseases, dementia, and even neoplasias in different organ systems. This spectrum of developmental anomalies and constitutional diseases may be linked to high-risk conceptions related to preovulatory overripeness ovopathy (PrOO). Some developmental anomalies, such as NTDs, are to a large extent prevented by supplementation of folic acid before conception, but supplementation does not seem to prevent cardiovascular disease or cognitive decline. These diverging results can be elucidated by introduction of the PrOO concept, as MTHFR polymorphisms and inherent low folate levels induce both non-optimal maturation of the oocyte and unsuccessful DNA methylation and demethylation, i.e. epigenetic mutations. The PrOO concept is testable and predicts in a random population the following: (1) female carriers of specific genetic MTHFR variants exhibit more ovulatory disturbances and inherent subfecundity traits, (2) descendents from a carrier mother, when compared with those from a wild-type mother, are more frequently conceived in PrOO high-risk conditions and, thus, (3) disadvantaged in life expectancy. If so, some MTHFR polymorphisms represent a novel, genetically determined, PrOO high-risk conception category comparable to those which are environmentally and behaviorly influenced. These high-risk conditions may cause developmental anomalies and defective epigenetic reprogramming in progeny. The interaction between genetic and environmental factors is a plausible mechanism of multifactorial inheritance.
PMCID: PMC2500045  PMID: 18616826
16.  Estrogen level monitoring in artificial frozen-thawed embryo transfer cycles using step-up regime without pituitary suppression: is it necessary? 
To discuss the meaning of serum oestradiol monitoring in frozen embryo transfer cycle using hormone replacement without pretreatment with gonadotropin hormone (GnRH) agonist.
The data from two hundred twelve women undergoing two hundred seventy-four frozen-thawed embryo transfer (FET) cycles was included in this retrospective cohort study. They were detected of serum oestradiol levels and endometrium thicknesses during hormone supplement FET cycles and compared their pregnancy outcomes according to their oestradiol level on progesterone initiation day.
Patients with different levels of serum oestradiol (percentile 0–25th, 25th–75th and 75th–100th) on progesterone initiation day yielded the endometrium thickness of 9.3 ± 0.12, 8.9 ± 0.07 and 9.1 ± 0.11 mm(P > 0.05) and the pregnancy rate of 32.2%, 38.4% and 36.3% (P > 0.05) respectively.
The serum estradiol level did not predict pregnancy success in hormone replacement FET cycles, suggesting that oestradiol monitoring in this method of endometrial preparation is unnecessary.
PMCID: PMC2467429  PMID: 18598369
17.  Review 
PMCID: PMC2432072
18.  Paternal effects on early embryogenesis 
Historically, less attention has been paid to paternal effects on early embryogenesis than maternal effects. However, it is now apparent that certain male factor infertility phenotypes are associated with increased DNA fragmentation and/or chromosome aneuploidies that may compromise early embryonic development. In addition, there is a growing body of evidence that the fertilizing sperm has more function than just carrying an intact, haploid genome. The paternally inherited centrosome is essential for normal fertilization, and the success of higher order chromatin packaging may impact embryogenesis. Epigenetic modifications of sperm chromatin may contribute to the reprogramming of the genome, and sperm delivered mRNA has also been hythesized to be necessary for embryogenesis. There is less information about the epigenetic factors affecting embryogenesis than genetic factors, but the epigenetics of gamete and early embryogenesis is a rapidly advancing field.
PMCID: PMC2397432  PMID: 18485208
19.  Pregnancy following homologous prepubertal ovarian transplantation in the dog 
In several canine models of hereditary human disease the homozygote dogs die prior to puberty, or have substantially reduced fertility. To create a clinically healthy animal that can be bred, but can also transmit the gene of interest, a model of homologous ovarian transplantation in prepubertal dogs was developed. Six dog leukocyte antigen (DLA) identical littermates underwent transplantation of ovarian cortical strips (n = 2) or the entire ovary (n = 4). Immunosuppression was maintained with cyclosporine and MMF in the immediate post-operative period and cyclosporine alone thereafter. All 6 dogs entered puberty and normal semiannual estrus cycles as demonstrated by both physical changes and increasing serum progesterone. Four dogs were bred to a proven stud male, and one became pregnant. Three viable fetuses with observable heartbeats were detected on ultrasound examination. Although the dog eventually aborted the litter, this work represents the first pregnancy achieved following a prepubertal ovarian transplant in the dog.
PMCID: PMC2365961  PMID: 18430233
20.  Monozygotic multiple gestation following in vitro fertilization: analysis of seven cases from Japan 
We present a series of monozygous multiple gestations achieved following in vitro fertilization (IVF): one case of monochorionic triplet pregnancy and six cases of dizygotic triplet pregnancy. From September 2000 to December 2006, all patients achieving clinical pregnancy by ART were reviewed (n = 2433). A 37 year-old woman who delivered a healthy singleton after IVF returned two years later for FET, and a single blastocyst was transferred. This also resulted in pregnancy, but TV-USG revealed a single gestational sac with three distinct amniotic sacs, each containing a distinct fetal pole with cardiac activity. This pregnancy was electively terminated at nine weeks' gestation. An additional six cases of dizygotic triplets established after fresh embryo transfer (no ICSI or assisted hatching) are also described. Of these, one resulted in a miscarriage at eight weeks' gestation and five patients have an ongoing pregnancy. This case series suggests the incidence of dizygotic/monochorionic triplets following IVF is approximately 10 times higher than the expected rate in unassisted conceptions, and underscores the importance of a conservative approach to lower the number of embryos at transfer. The role of embryo transfer technique and in vitro culture media in the twinning process requires further study.
PMCID: PMC2034589  PMID: 17888172
21.  Regional clinical practice patterns in reproductive endocrinology: A collaborative transnational pilot survey of in vitro fertilization programs in the Middle East 
This research describes current clinical and demographic features sampled from reproductive endocrinology programs currently offering in vitro fertilization (IVF) in the Middle East.
Clinic leadership provided data via questionnaire on patient demographics, demand for IVF services, annual cycle volume, indications for IVF, number of embryos transferred, twinning frequency, local regulations governing range of available adjunct therapies, time interval between initial enrollment and beginning IVF as well as information about other aspects of IVF at each center.
Data were received from representative IVF clinics (n = 13) in Cyprus, Egypt, Iran, Israel, Jordan, Lebanon, Qatar, Saudi Arabia and Turkey. Mean (± SD) age of respondents was 47.8 ± 8 yrs, with average tenure at their facility of 11.2 ± 6 yrs. Estimated total number of IVF programs in each nation responding ranged from 1 to 91. All respondents reported individual participation in accredited CME activity within 24 months. 76.9% performed embryo transfers personally; blastocyst transfer was available at 84.6% of centers. PGD was offered at all sites. In this population, male factor infertility accounted for most IVF consultations and the majority (59.1%) of female IVF patients were < 35 yrs of age. Prevalence of smoking among female IVF patients was 7.2%. Average number of embryos transferred was 2.4 (± 0.4) for patients at age < 35 yrs, and 2.9 (± 0.8) at age > 41 yrs. For these age categories, twinning (any type) was observed in 22.6 (± 10.8)% and 13.7 (± 10.4)%, respectively. In 2005, the average number of IVF cycles completed at study sites was 1194 (range 363–3500) and 1266 (range 263–4000) in 2006. Frozen embryo transfers accounted for 17.2% of cycles at these centers in 2005. Average interval between initial enrollment and IVF cycle start was 8 weeks (range 0.3–3.5 months).
This sampling of diverse IVF clinics in the Middle East, believed to be the first of its kind, identified several common factors. Government registry or oversight of clinical IVF practice was limited or nonexistent in most countries, yet number of embryos transferred was nevertheless fairly uniform. Sophisticated reproductive health services in this region are associated with minimal delay (often < 8 weeks) from initial presentation to IVF cycle start. Most Middle East nations do not maintain a comprehensive IVF database, and there is no independent agency to collect transnational data on IVF clinics. Our pilot study demonstrates that IVF programs in the Middle East could contribute voluntarily to collaborative network efforts to share clinical data, improve quality of care, and increase patient access to reproductive services in the region.
PMCID: PMC2041947  PMID: 17725823
22.  Deciding the fate of disputed embryos: ethical issues in the case of Natallie Evans 
A number of disputes have arisen in recent years over the status of non-transferred embryos cryopreserved during in vitro fertilisation. One such case is that of Natallie Evans who in April 2007 lost her final attempt to prevent the destruction of embryos created with the sperm of her former partner. Ms Evans had been rendered infertile by cancer treatment, and the embryos represented her only chance of having genetically related children.
Arguments over stored embryos often conflate different concepts of parenthood. The effects of 'forcing' genetic parenthood on a man are mistakenly presented as being analogous with forcing women to bear children. Likewise, there is a tendency to assume that genetic parenthood necessarily involves legal, financial and psychological implications. Men (or women) who object to becoming parents should be encouraged to specify which aspects of parenthood they regard as being harmful. While the financial or physical burdens of forced parenthood involve objective harms, the putative psychological harms of enforced genetic parenthood are subjective, and this distinction should be recognised. Popular beliefs about genetic parenthood perpetuate the kinds of subjective concerns expressed by Ms Evans' partner, but the concept of genetic parenthood itself may come under pressure in the face of future technological developments.
Historical legal requirements obliging men to provide for their genetic offspring still pervade in the law. These perceptions are becoming outmoded in context of rapidly-moving reproductive technologies. To avoid disputes greater flexibility is required. The economic and legal components of parenthood should be negotiable in cases where disputes arise, and should not be assumed to flow inexorably from genetic paternity. To reduce the chances of disputes arising, consent protocols for cryopreservation of non-transferred embryos should be refined. Couples should address the possibility of divorce or the breakup of their relationships, and should be made aware that embryos can be destroyed at the behest of either party in these circumstances.
PMCID: PMC1936431  PMID: 17610737
23.  Serum estradiol/progesterone ratio on day of embryo transfer may predict reproductive outcome following controlled ovarian hyperstimulation and in vitro fertilization 
To determine whether estradiol-to-progesterone (E2/P) ratios at the time of embryo transfer (ET) have an effect on implantation and pregnancy in IVF cycles.
239 women consecutively treated by IVF or ICSI were retrospectively analyzed and early luteal serum E2 and P were measured on the day of ET. Transfer occurred after a variable in vitro culture period ranging from 4–7 days after ovulation induction (OI). Following ET, serum E2/P ratios were calculated for clinical pregnancies, preclinical abortions and non-coneption cycles.
Receiver-operator curve analysis demonstrated that the E2/P ratio could differentiate between clinical pregnancies and non-pregnant cycles (area under the curve on OI +4 days = 0.70; 95% CI = 0.60–0.80; p = 0.003, on OI +5 days = 0.76; 95% CI = 0.64–0.88; p = 0.001, OI +7 days = 0.85; 95% CI = 0.75–0.96; p < 0.0001).
These retrospective data may hold prognostic value regarding endometrial receptivity as reflected by E2/P measurements and may help improve IVF treatment outcome. Further prospective studies should be undertaken to confirm these obersveration.
PMCID: PMC1832209  PMID: 17371588
24.  Clinical applications and limitations of current ovarian stem cell research: a review 
The publication of a report in Nature in 2004 by the Tilly group suggesting that mouse ovaries are capable of generating oocytes de novo post-natally, has sparked interest in a problem long thought to have been resolved from classical studies in a variety of mammalian species. Within a nearly two year time period, laboratories around the world have taken up the challenge to dogma raised by this initial report, either to test this concept in an experimental basic science setting or give direction to clinical applications that could result, were the original premises of this work in the mouse valid for extrapolation to humans. This review provides a status report for this promising area of research, (1) to summarize recent findings in the literature with respect to the validity of the original hypothesis proffered by the Tilly group, and, (2) to gauge the potential utility of ovarian stem cells as a treatment for certain forms of human infertility.
PMCID: PMC1553467  PMID: 16872542
25.  No advantage of laser-assisted over conventional intracytoplasmic sperm injection: a randomized controlled trial [NCT00114725] 
Intracytoplasmic sperm injection (ICSI) is a component of infertility treatment often employed when conventional in vitro fertilization is unlikely to be successful. Despite good clinical results with ICSI, the procedure is typically associated with degeneration of a significant percentage (approximately 10%) of the treated oocytes. The cause of this degeneration remains unclear. Speculation that damage caused by oocyte compression during the injection procedure may be responsible has led to the development of a novel technique known as laser-assisted ICSI. This procedure involves drilling a small hole through the zona pellucida with a laser prior to sperm injection. Preliminary studies have suggested that laser-assisted ICSI may dramatically reduce oocyte degeneration rates. The objective of this study was to examine whether the reported benefits of laser-assisted ICSI could be verified on a larger, less-selected group of patients.
Oocytes retrieved from 59 patients scheduled for ICSI were randomly divided into equal treatment and control groups. Oocytes in the treatment group were inseminated by laser-assisted ICSI, while oocytes in the control group were inseminated by conventional ICSI. Outcome variables (oocyte fertilization and degeneration, embryo cell numbers and fragmentation on days 2 and 3, and compaction and blastocyst formation rates) were compared between treatment and control groups by paired-sample t-test. Subgroup analysis was performed according to zona pellucida and oolemma breakage patterns.
No significant differences between treatment and control groups were observed for any of the measured outcome variables. However, fragile zonae pellucidae were associated with significantly poorer embryo quality, and fragile oolemmas that broke easily upon insertion of the injection needle were associated with a significantly higher oocyte degeneration rate. Nevertheless, there were also no between-treatment differences in clinical outcomes within these patient subpopulations.
Contrary to previous reports based on smaller sample sizes, the results of this study suggest that there is no benefit of laser-assisted ICSI, either for the general population of ICSI patients, or for patients prone to zona pellucida or oolemma fragility.
PMCID: PMC1550249  PMID: 16822317

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