Day 5 vitrified blastocyst transfer versus day 6 vitrified blastocyst transfer in oocyte donation program.

The superiority of day 5 blastocysts compared to day 6 blastocysts in fresh cycle transfers was previously demonstrated and attributed mainly to endometrial asynchrony. Data from frozen blastocysts transfers showed conflicting results, possibly due to heterogeneous patient population and embryo quality. The aim of this study was to compare clinical pregnancy rate (CPR) and live birth rate (LBR) between transfers of vitrified day 5 blastocysts and day 6 blastocysts in oocyte donation, blastocyst-only cycles. In a retrospective, multi-center study, with a single oocyte donation program, a total of 1840 frozen embryo transfers (FET's) were analyzed, including 1180 day 5 blastocysts and 660 day 6 blastocysts transfers. Day 5 blastocyst transfers had better embryonic development and significantly higher CPRs (34.24% vs. 20.15%, P < 0.0001), higher LBRs (26.89% vs. 14.77%, P < 0.0001), less cycles to LBR (1.83 ± 0.08 vs. 2.39 ± 0.18, P = 0.003) and shorter time to LBRs (76.32 ± 8.7 vs. 123.24 ± 19.1 days, P = 0.01), compared to day 6 transfers, respectively. A multivariate stepwise logistic regression indicated, that day 5 transfer was an independent factor for CPRs (OR 1.91; 95% CI 1.43-2.54, P < 0.001) and LBRs (OR 2.26; 95% CI 1.19-4.28, P = 0.01), regardless of embryo quality, compared to day 6. In conclusion, day 5 blastocysts in oocyte donation program have significantly higher CPRs and LBRs, and present shorter time to delivery, compared to day 6 blastocysts, regardless of embryo quality.

What is the best treatment for women with polycystic ovarian syndrome and high LH/FSH ratio? A comparison among in vitro fertilization with GnRH agonist, GnRH antagonist and in vitro maturation.

PURPOSE: To evaluate whether high LH/FSH ratio has a clinical impact on patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) with GnRH-agonist/antagonist protocols or in vitro maturation (IVM) treatments. METHODS: We retrospectively reviewed all PCOS patients with day 3 LH/FSH ratio ≥1.5 who underwent IVF or IVM. The main outcomes measures were embryo quality and pregnancy rate. RESULTS: A total of 75 cycles were included. Among these, 44 patients underwent long agonist protocol, 16 antagonist protocol and 15 IVM. Age, basal LH and FSH levels, as well as duration of infertility were comparable for all groups. The LH level on the day of hCG administration was significantly lower in the antagonist group (0.9 IU/ml) compared to the long agonist group (1.4 IU/ml, p = 0.01). There was no difference in pregnancy rates among the groups: 27.2 % in the long agonist group, 37.5 % in the antagonist group and 26.6 % among the IVM patients. CONCLUSIONS: High LH/FSH ratio had no adverse effect on pregnancy rates in all three treatment modes.

Assessment of sperm hyperactivated motility and acrosome reaction can discriminate the use of spermatozoa for conventional in vitro fertilisation or intracytoplasmic sperm injection: preliminary results.

Basic semen analysis is insufficient for determining the fertility potential. The aim of this study was to determine if hyperactivated motility (HAM) and acrosome reaction (AR) can be useful tests for evaluating semen quality during male infertility evaluations and to help the clinician decide whether regular insemination or intracytoplasmic sperm injection (ICSI) is preferable during in vitro fertilisation. A prospective study was conducted. Patients with normal sperm according to World Health Organization guidelines who underwent IVF treatment and planned regular insemination were asked to participate. A portion of sperm sample was evaluated for HAM and AR on day of ovum pick up. In HAM assessment, 93.3% of patients with increased HAM had a high fertilisation rate compared with 64% in the group without increased HAM (P = 0.059). For the AR evaluation, 91.7% of samples with a low rate of spontaneous AR had a high fertilisation rate compared with 39.3% in the group with a high rate of spontaneous AR (P = 0.004).

Age and infertility: the clinical point of view.

With the demands of the modern western world of today, women delay the conception of their first child and this adversely impacts on their fertility. Vast attempts have been made to diagnose and counter ageing women infertility. In this literature review article, we bring forward theories which may account for the age-related decline of fertility and explained about the assessment and treatment modalities currently available. After concluding that ovarian stimulation with the use of gonadotrophins and clomiphene citrate is not useful in women of 40 year and over, it leaves us with in-vitro fertilization as the most suitable method of increasing the rate of successful pregnancies and live birth rates. It is important to campaign the effects age has on fertility since, even highly educated women, are not aware of the full impacts age has on fertility.

Re-evaluation of post-wash sperm is a helpful tool in the decision to perform in vitro fertilisation or intracytoplasmic sperm injection.

The aim of this study was to find discriminatory parameters, based on sperm characteristics on the day of ovum pickup, that can help guide the decision to perform either intracytoplasmic sperm injection (ICSI) or in vitro fertilisation (IVF). We evaluated 112 cycles fertilised with both regular and ICSI insemination during the same cycle. A total of 112 cycles were analysed. In 62 cycles, fertilisation was obtained with both ICSI and IVF, and in 50 cycles, fertilisation was obtained by ICSI alone. The sperm samples were re-evaluated after the preparation process. The mean initial total motile sperm count (TMSC) was 66.3 × 10(6) ± 47.5 in the group that underwent both methods and 23.1 × 10(6) ± 20.4 in the ICSI only group (P < 0.05). After sperm preparation, the mean post-wash TMSC was 4.4 × 10(6) ± 3.4 and 1.06 × 10(6) ± 0.9 respectively (P < 0.05). A cutoff of 1.5 × 10(6) or fewer sperm after preparation as an indicator for ICSI has a sensitivity of 80% and a specificity of 77%. Re-evaluation of TMSC can prevent unexpected fertilisation failure. Fewer than 1.5 million TMSC after wash should be considered an indication for ICSI fertilisation.

Light-mediated activation reveals a key role for protein kinase A and sarcoma protein kinase in the development of sperm hyper-activated motility.

BACKGROUND: Hyper-activated motility (HAM) is part of the sperm capacitation process, which is necessary for fertilization. In this study, we investigated the effect of visible light on sperm motility and hyperactivation and evaluated pathways mediating these effects. METHODS: Human sperm (1 × 107 cells/ml) in capacitation media were irradiated for 3 min with 40 mW/cm² visible light (400-800 nm with maximum energy at 600 nm). Sperm motility was assessed and analyzed by computer-assisted sperm analysis. The involvement of sperm capacitation factors was investigated as follows. The generation of reactive oxygen species (ROS) was measured using 20,70-dichlorofluorescein diacetate. Protein kinase A (PKA) and sarcoma protein kinase (Src) activity were measured using western blot analysis and inhibited using 50 µM H89 and 10 µM PP2, respectively. Soluble adenlyl cyclase was inhibited using 20 µM 2-OH-Estradiol. The intracellular concentration of free Ca(2+) was assessed using the fluorescent calcium indicator, Fluo-4/AM. Sperm DNA fragmentation was determined using the sperm chromatin dispersion test. RESULTS: Light irradiation of human sperm caused a significant increase in hyper-HAM but not total motility. The production of ROS and activation of soluble adenylyl cyclase and PKA mediated the effect of light on HAM. Light irradiation also activated Src, and inhibition of Src significantly reduced the effect of light on HAM. Light irradiation caused a rapid increase in intracellular Ca²âº concentration and the increase in HAM was significantly reduced when voltage-dependent-Ca²âº-channel activity was blocked or when Ca²âº-deficient medium was used. CONCLUSIONS: Light irradiation of human sperm for a short time causes a significant increase in HAM in a mechanism mediated by ROS production, activation of PKA, Src and Ca²âº influx.

IVF outcome with cryopreserved testicular sperm.

The introduction of intracytoplasmic sperm injection and the use of spermatozoa extracted from the testicles have changed the option for conception for azoospermic patients. The purpose of the present study was to evaluate the IVF outcome after using cryopreserved testicular sperm samples in comparison with fresh ones. A total of 667 in vitro fertilisation cycles with fresh or cryopreserved testicular sperm obtained by an open biopsy and testicular needle aspiration were evaluated. Sperm motility was present in 70.9% of the cycles in Group-I, 77.8% cycles in Group-II and in 83.3% In Group-III (NS). The fertilisation rates were similar in the three study groups (50%, 48.6% and 54.8% respectively). The pregnancy rates were 26.7%, 22.2% and 16.3% respectively (NS). The delivery rate, however, was significantly lower in Group-III (4.1%) than in Group-I and -II (18.4% and 15.9%, respectively, P < 0.05). The IVF results after use of cryopreserved testicular sperm are comparable with those obtained with the fresh specimens. Lack of sperm motility before cryopreservation does not exclude favourable outcome and therefore testicular sperm freezing is feasible whenever there are enough sperm cells in the extracted testicular tissue.

Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study.

BACKGROUND: The aim of this study was to evaluate the effect of dehydroepiandrosterone (DHEA) supplementation on in vitro fertilization (IVF) data and outcomes among poor-responder patients. METHODS: A randomized, prospective, controlled study was conducted. All patients received the long-protocol IVF. Those in the study group received 75 mg of DHEA once a day before starting the next IVF cycle and during treatment. RESULTS: Thirty-three women with significantly diminished ovarian reserves were enrolled, 17 in the DHEA group and 16 in the control group. The 33 patients underwent 51 IVF cycles. The DHEA group demonstrated a non-significant improvement in estradiol levels on day of hCG (P = 0.09) and improved embryo quality during treatment (P = 0.04) between first and second cycles. Patients in the DHEA group also had a significantly higher live birth rate compared with controls (23.1% versus 4.0%; P = 0.05), respectively. Six of seven deliveries were among patients with secondary infertility (P = 0.006). CONCLUSION: Dehydroepiandrosterone supplementation can have a beneficial effect on ovarian reserves for poor-responder patients on IVF treatment. Clinicaltrials.gov: NCT01145144.

Does age at orchidopexy impact on the results of testicular sperm extraction?

The aim of this study was to evaluate the affect of age at the time of orchidopexy on testicular sperm extraction (TESE) results among patients with a history of cryptorchidism and azoospermia. This retrospective study compared TESE results for couples undergoing IVF treatment, among two groups of patients. Group A included patients who underwent orchidopexy at age 10 and younger, and group B included patients who had the procedure above the age of 10. A total of 42 patients were included in the study. Forty patients had bilateral cryptorchidism and two had unilateral. The overall rate of sperm recovery was 59.5%. No differences were found in the sperm retrieval, fertilization, implantation, pregnancy, or live birth rates between the groups. The results suggest that age at orchidopexy, either at 10 years of age or younger or above 10 years of age, was not a predictive factor for successful TESE. Although bilateral cryptorchidism is usually considered a testicular secretory dysfunction, it was found that sperm retrieval attempts yielded spermatozoa in almost 60% of patients with azoospermia and a history of cryptorchidism.

Gestational diabetes insipidus and intrauterine fetal death of monochorionic twins.

Gestational diabetes insipidus (GDI) is a rare disorder. The onset is usually in the third trimester of pregnancy. We present a 24-year-old primigravida in her 35th week of a monochorionic-diamniotic twin pregnancy. The patient presented with intrauterine death of both twins accompanied by HELLP syndrome, hypernatremia and hemoconcentration. Urine osmolality below that of the plasma suggested GDI. 1-deamino-8D-arginine vasopressin (dDAVP) treatment was started with a quick response. GDI is probably the result of excessive activity of placental vasopressinase. In cases of liver dysfunction, the clearance rate of vasopressinase decreases, explaining the association of GDI with acute fatty liver and HELLP syndrome. Alert to this diagnosis, its evaluation and treatment is important.

Maternal serum adiponectin levels during human pregnancy.

OBJECTIVE: Pregnancy is a unique situation characterized by insulin resistance. The role of adiponectin, an insulin-sensitizing hormone, has not been completely clarified during pregnancy. The aim of this cross-sectional study was to evaluate adiponectin levels during pregnancy and postpartum. STUDY DESIGN: Adiponectin and leptin levels were tested in 80 pregnant women, 20 in each trimester (mean gestational age 10.5+/-1.9; 19.3+/-4.9; 39.3+/-0.8 weeks,) as well as 4 days postpartum. RESULTS: Adiponectin levels during first (13.3+/-3.6 micro g/ml), second (12.6+/-4.4 micro g/ml) and third trimester (11.2+/-3.7 micro g/ml) did not differ and were significantly higher than postpartum levels (8.8+/-2.1 micro g/ml; P<0.0001, P<0.004 and P<0.02, respectively). CONCLUSION: Despite increased insulin resistance during pregnancy, no significant alterations in adiponectin levels were observed. This may imply that the regulation of adiponectin during gestation is altered. The elevated gestational adiponectin levels are consistent with increased 'adiponectin resistance' during pregnancy.

Elevated day 3 FSH/LH ratio due to low LH concentrations predicts reduced ovarian response.

Adequate ovarian response, essential for successful IVF, cannot be accurately predicted. This study retrospectively reviewed all patients undergoing IVF from 1998 to 2001. Inclusion criteria were age <41 years at treatment onset and a basal day 3 serum FSH concentration <12 IU/l. Women with FSH or=3 in group 1 and <3 in group 2 (controls). Age at treatment initiation, basal serum day 3 FSH and LH concentrations, peak serum oestradiol concentration, number of retrieved and fertilized oocytes and pregnancy rate were analysed. Groups 1 (n = 41, 111 IVF treatment cycles) and 2 (n = 596, 1,434 IVF treatment cycles) were similar in term of woman's mean age. Group 1 had significantly higher mean basal day 3 FSH concentration (P < 0.01) and significantly lower oestradiol concentrations at oocyte retrieval (P < 0.01), mean number of oocytes retrieved and fertilized (P < 0.01) and pregnancy rate (P = 0.016). The same trend persisted after excluding 98 patients with basal FSH concentrations >8 IU/l. In conclusion, elevated day 3 FSH/LH ratio is associated with an inferior outcome in IVF treatment cycles and may be used as an additional predictor for decreased ovarian response.

Importance of accurate preoperative diagnosis in the management of aggressive angiomyxoma: report of three cases and review of the literature.

BACKGROUND: Aggressive angiomyxoma is a benign but locally aggressive tumor that occurs mostly in young women. Because excision is often incomplete, the risk of local recurrence is high. This report describes differences in presentation and the importance of accurate preoperative diagnosis of this rare neoplasm. METHODS AND RESULTS: We describe three cases with different presentations. Two were initially misdiagnosed, and local recurrence necessitated reoperation. Accurate diagnosis in the third case was followed by complete excision, with no recurrence. CONCLUSION: Aggressive angiomyxoma should be considered in the differential diagnosis of young women who present with a well-defined mass in the pelvic tissue. Accurate preoperative diagnosis should alert the surgeon to the need for wide excision, which is essential for prevention of local recurrence.

Outcome of pregnancies complicated by severe ovarian hyperstimulation syndrome (OHSS): a follow-up beyond the second trimester.

UNLABELLED: The main aim of this study was to assess the obstetric complications for those pregnancies that are complicated by ovarian hyperstimulation syndrome (OHSS) and continue beyond the first trimester. We checked also for other related serious events that occurred during the first trimester. METHODS: We included only patients whose pregnancies continued beyond the first trimester and compared them with IVF-treated patients displaying moderate ovarian response. RESULTS: We studied 165 patients with OHSS (101 singletons and 64 twins) and 156 IVF control patients (85 singletons and 71 twins). Two serious complications, gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH), were noted in both groups. However, the incidence of these two complications did not differ significantly between the groups. In the OHSS group, GDM presented with an incidence of 9.9% for singletons and 9.4% for twins, and 12.9% and 7.0%, respectively, for the control group. PIH presented as 6.9% for singletons and 10.9% for twins in the OHSS group, and 8.2% and 7.0%, respectively, for the control groups. During the first trimester laparoscopies for suspected ovarian torsion were performed in 13 patients, and in 10 patients the diagnosis were confirmed. CONCLUSIONS: Although patients with OHSS-complicated pregnancies previously reported a relatively high risk of GDM and PIH, the occurrence rates do not differ from a matched control group of normally responding patients who conceived after IVF.

[Aromatase inhibitors--new applications in gynecology].

P-450 aromatase inhibitors, designed for suppressing estradiol production, were first approved for the treatment of advanced breast cancer. Recent studies have provided evidence that aromatase inhibitors may be effective in the short term for induction of ovulation and in the long-term for treatment of endometriosis. Based on current data, the role of aromatase inhibitors in the management of various gynecological conditions may soon be widely determined.

Neural basis of novel and well-learned recognition memory in schizophrenia: a positron emission tomography study.

The level of familiarity of a given stimulus plays an important role in memory processing. Indeed, the novelty/familiarity of learned material has been proven to affect the pattern of activations during recognition memory tasks. We used visually presented words to investigate the neural basis of recognition memory for relatively novel and familiar stimuli in schizophrenia. Subjects were 34 healthy volunteers and 19 schizophrenia spectrum patients. Two experimental cognitive conditions were used: 1 week and again 1 day prior to the PET imaging subjects had to thoroughly learn a list of 18 words (well-learned memory). Subjects were also asked to learn another set of 18 words presented 1 min before the PET experiment (novel memory). During the PET session, subjects had to recognize the list of 18 words among 22 new (distractor) words. Subjects also performed a control task (reading words). A nonparametric randomization test and a statistical t-mapping method were used to determine between- and within-group differences. In patients the recognition of novel material produced relatively less flow in several frontal areas, superior temporal gyrus, insular cortex, and parahippocampal areas, and relatively higher activity in parietal areas, visual cortex, and cerebellum, compared to controls. No significant differences in flow were seen when comparing well-learned memory activations between groups. These results suggest that different neural pathways are engaged during novel recognition memory in patients with schizophrenia compared to healthy individuals. During recognition of novel material, patients failed to activate frontal/limbic regions, recruiting a set of posterior perceptual brain regions instead.

Novel vs. well-learned memory for faces: a positron emission tomography study.

Previous work has suggested that familiarity/novelty of learned materials affects the circuitry involved in memory, primarily in the size of activations rather than the pattern of activation. Although this work has examined both recall and recognition, it has been limited to verbal material. In this study, we set out to determine if the same result applies to nonverbal memory. We used the same experimental design, but used faces as the memory task. Healthy volunteers thoroughly learned a set of 18 faces a week prior to the Positron Emission Tomography (PET) experiment (well-learned memory) and were asked to remember another set of 18 faces, to which they were exposed 1 min before the PET experiment (novel memory). During the PET session, their task was to recognize the faces learned a week before and the faces seen a minute before; the "remembered faces" were interspersed among entirely new (distractor) faces. We found that, unlike for verbal material, the retention interval and the familiarity level of the faces affected both the pattern and the size of activations. Comparing the novel and well-learned recognition tasks revealed that novel memory for faces is primarily a frontal-lobe task, while well-learned recognition memory for faces utilizes a more distributed neural circuit, including visual areas, which appear to serve as memory-storage sites.

Human frontal cortex: an MRI-based parcellation method.

The frontal lobe is not a single anatomical and functional brain region. Several lines of research have demonstrated that particular subregions within the frontal lobe are associated with specific motor and cognitive functions in the human being. Our main purpose is to develop a magnetic resonance image (MRI)-based parcellation method of the frontal lobe that permits us to explore plausible abnormalities in functionally relevant frontal subregions in brain illnesses. We describe a procedure using MRI for subdividing the entire frontal cortex into 11 subregions: supplementary motor area (SMA), rostral anterior cingulate gyrus (r-ACiG), caudal anterior cingulate gyrus (c-ACiG), superior cingulate gyrus (SCiG), medial frontal cortex (MFC), straight gyrus (SG), orbitofrontal cortex (OFC), precentral gyrus (PCG), superior frontal gyrus (SFG), inferior frontal gyrus (IFG), and middle frontal gyrus (MFG). Our method posits to conserve the topographic uniqueness of individual brains and is based on our ability to visualize both the three-dimensional (3D) rendered brain and the three orthogonal planes simultaneously. The reliability study for gray matter volume and surface area of each subregion was performed on a set of 10 MR scans by two raters. The intraclass R coefficients for gray matter volume of each subregion ranged between 0.86 and 0.99. We describe here a reproducible and reliable topography-based parcellation method of the frontal lobe that will allow us to use new approaches to understand the role of particular frontal cortical subregions in schizophrenia and other brain illnesses.

Direct comparison of the neural substrates of recognition memory for words and faces.

For the purpose of identifying the relatively specific brain regions related to word and face recognition memory on the one hand and the regions common to both on the other, regional cerebral blood flow associated with different cognitive tasks for recognition memory was examined using [H215O]PET in healthy volunteers. The tasks consisted of recognizing two types of stimuli (faces and words) in two conditions (novel and familiar), and two baseline tasks (reading words and gender classification). The statistical analyses used to identify the specific regions consisted of three subtractions: novel words minus novel faces, familiar words minus familiar faces, and reading words minus gender classification. These analyses revealed relative differences in the brain circuitry used for recognizing words and for recognizing faces within a defined level of familiarity. In order to find the regions common to both face and word recognition, overlapping areas in four subtractions (novel words minus reading words, novel faces minus gender classification, familiar words minus reading words, and familiar faces minus gender classification) were identified. The results showed that the activation sites in word recognition tended to be lateralized to the left hemisphere and distributed as numerous small loci, and particularly included the posterior portion of the left middle and inferior temporal gyri. These regions may be related to lexical retrieval during written word recognition. In contrast, the activated regions for face recognition tended to be lateralized to the right hemisphere and located in a large aggregated area, including the right lingual and fusiform gyri. These findings suggest that strikingly different neural pathways are engaged during recognition memory for words and for faces, in which a critical role in discrimination is played by semantic cueing and perceptual loading, respectively. In addition, the investigation of the regions common to word and face recognition indicates that the anterior and posterior cingulate have dissociable functions in recognition memory that vary with familiarity, and that the cerebellum may serve as the co-ordinator of all four types of recognition memory processes.