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Should a patient's own IVF physician perform the embryo transfer?

PURPOSE: To compare pregnancy rates of embryo transfers performed by a patient's own IVF physician to pregnancy rates of embryo transfers performed by other physicians on the IVF team. METHODS: Retrospective cohort study; University hospital. RESULTS: A total of 3029 embryo transfers were included. 434 patients (14%) had an embryo transfer by their own IVF physician. There was no difference in pregnancy rates comparing patients who had embryos transferred by a different physician than their own IVF physician when all cycle attempts were analyzed [Odds ratio (OR) 1.1; Confidence interval (CI) 0.9-1.4]. There was no significant difference between the groups' population characteristics. A subset analysis of 1st cycle only embryo transfers (n=1416) also revealed no difference in pregnancy rates [OR 1.1; CI 0.8-1.5]. CONCLUSIONS: Patients can be reassured that their chances of pregnancy are the same whether their embryo transfer is performed by their own physician or another physician in the practice.

Embryo Transfer↗

Reproduction as spiritual kin work: orthodoxy, IVF, and the moral economy of motherhood in Greece.

Bringing gender and kinship studies together with an anthropology of religion, in this article I demonstrate how urban Greek couples and clinical practitioners in the middle 1990s proceeded with in vitro fertilization (IVF) in the absence of government regulations, and did so with reference to cultural beliefs and social relations consistent with Greek Orthodox religious practice. Drawing on ethnographic observations at an Athens IVF clinic as well as on interviews with former patients, I argue that Athenian women, in particular, engage IVF as a kind of spiritual kin work, normalizing the use of medical techniques with reference to ideologies of motherhood that treat it as a woman's moral achievement and as a source of womanly suffering. Since the period of ethnographic research described here, and despite disapproval of the Greek Orthodox Church, legislation regulating the use of IVF and other methods of medically assisted reproduction has become law. This article reconciles how the Church can officially reject medically assisted means of reproduction that Athenian users have normalized with reference to spiritual beliefs and practices.

Attitude to Health↗

IVF: induction of ovulation in poor responders.

All IVF programs have a consistent rate of failure in inducing ovulations. Pharmacological induction of ovulation is otherwise crucial for an IVF program because of the need for more than one ovum. Since it is well known that the best candidates for HMG treatment are hypogonadotropic women a short reversible hypogonadotropic state was induced in IVF patients by LH-RH agonist (Buserelin). Superovulation was then achieved with very high initial doses of FSH (Metrodin) in order to maximize the ovarian response. This technique used in 116 IVF women induced a satisfactory follicle growth even in 70% of the patients already poorly responsive to HMG stimulation.

Adult↗

Effect of human leukemia inhibitory factor on in vitro development of IVF-derived bovine morulae and blastocysts.

This study was conducted to investigate whether human leukemia inhibitory factor (hLIF) improves the subsequent development of IVF-derived bovine morulae and blastocysts. To obtain IVF-derived bovine morulae, ova were matured and fertilized in vitro and cultured in 0.5 ml of synthetic oviduct fluid (SOF) medium supplemented with 10% human serum (HS) for 5 d at 39 degrees C under a gas atmosphere of 5% CO(2), 5% O(2), 90% N(2). Morulae and early blastocysts at Day 5 of culture were cultured in 0.5 ml of SOF medium with or without 5000 U/ml recombinant hLIF for 2 or 3 d (2 groups). To investigate the effect of addition of hLIF on the subsequent development of morulae, SOF medium was supplemented with 8 mg/ml BSA instead of HS. To test whether hLIF affects the subsequent development of IVF-derived bovine blastocysts, only good blastocysts that developed from SOF medium with or without hLIF at Days 7 and 8 of culture were frozen by a conventinal slow freezing method and again cultured in SOF medium with or without the addition of hLIF for 3 d after thawing (4 groups). Survival of frozen-thawed bovine embryos was evaluated for re-expansion and hatching of blastocysts during 3 d of culture. There was no significant difference in the developmental rate of Day 5 embryos to blastocysts between those cultured with (47.8%) and without (47.6%) addition of hLIF. However, the addition of hLIF before freezing significantly increased the hatching rate of IVF-derived bovine morulae (P < 0.05), whereas addition of hLIF after thawing did not increase the subsequent development of blastocysts. These results suggest that hLIF added at the Day 5 morula stage may contribute to bovine embryonic development through the hatching process.

Journal Article↗

A comparison of BoviPure and Percoll on bull sperm separation protocols for IVF.

In the present study, we have examined the effect of density gradient preparations BoviPure and Percoll on bull sperm separation and the in vitro fertilization (IVF) and culture (IVC) results. Frozen/thawed semen from five simmental bulls were pooled. Sperm quality parameters such as sperm motility, concentration, membrane activity (HOS assay), membrane integrity (SYBR-14/PI assay) and acrosomal status (EthD-1/FITC-PSA assay) were evaluated before and after sperm processing for IVF using BoviPure and Percoll density gradient separations. The results of the evaluated parameters before sperm processing were: motility 50%, concentration 82.33x10(6)spz/mL, membrane activity 39.05%, membrane integrity 42.97% and the acrosomal status 46.90% of the live spermatozoa with intact acrosomes. After sperm processing with BoviPure and Percoll the motility was 66.67 and 64.17%, the concentration was 25.50x10(6) and 27.67x10(6)spz/mL, the membrane activity was 53.78 and 56.58%, the membrane integrity was 70.85 and 68.76% of and the acrosomal status was 74.16 and 67.46% of the live spermatozoa with intact acrosomes, respectively. Percentages were referred to the total number of spermatozoa. There were significant differences (P<0.05) between the evaluated parameters before and after sperm processing for both separation protocols. We found no significant differences (P>0.05) regarding sperm evaluation parameters between the protocols. A total of 492 oocytes were matured and fertilized in vitro and cultured in SOFaaBSA in six replicates. The cleavage (D2) and blastocysts (D7) rate were significantly higher (P<0.05) for the BoviPure group compared to the Percoll group: 75.80 and 28.21%; 61.58 and 20.83%, respectively. However, the number of hatched blastocysts (D10) did not differ significantly between sperm separation protocols (P>0.05). Our results indicate that both protocols gave suitable sperm for IVF. This finding and the similarity between those two density gradient preparations suggests that BoviPure is a good alternative for sperm separation in bovine IVF.

Animals↗

Outcomes of IVF conceptions: are they different?

Perinatal outcomes, such as preterm delivery, low birth weight and some obstetric complications, are increased significantly after in-vitro fertilization (IVF) compared with spontaneously conceived pregnancies. The degree of difference is greater for singletons than for twins, especially with regard to preterm delivery which is increased two fold in IVF singletons and by 40% in twins. It is difficult to obtain accurate outcome information because of unmeasured confounders such as smoking status and fetal reduction. It is also unknown whether IVF technologies or patient infertility is the major contributor to adverse outcomes. Birth defects are increased, shown in a number of systematic reviews, and there has been a particular interest in imprinting syndromes. Epigenetic modifications may play a larger role in IVF outcomes, as yet unidentified. There is no apparent increase in adverse outcomes in children up to adolescence, although further studies are needed to examine longer-term risks, including those for cancer.

Abnormalities, Multiple↗

Age dependent assessment of TFPI levels in follicular fluid of women undergoing IVF.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type serine proteinase inhibitor which plays a central role in the extrinsic pathway of blood coagulation. A significant role of TFPI for the follicular development has been discussed in recent studies, and thrombotic complications during IVF procedure are a common problem. To elucidate the pathophysiological mechanisms underlying these problems, we have measured TFPI levels in human follicular fluid (hFF) of women undergoing in vitro fertilisation (IVF). METHODS: Total TFPI concentrations were determined in hFF of 28 women undergoing IVF treatment, 6 of whom developed an ovarian hyperstimulation syndrome (OHSS). RESULTS AND CONCLUSIONS: This is the first study to demonstrate an age-dependance of TFPI concentrations in hFF. Additionally, TFPI levels in hFF of women developing OHSS were determined as 323+/-66.8 ng/mL (mean+/-SD) in comparison with 279+/-137 ng/mL for non-OHSS patients. Our findings demonstrate that, unlike the decreased TFPI levels found in OHSS patients' blood, there is no statistically significant difference in hFF TFPI levels between OHSS and non-OHSS patients. Furthermore, we could show that the outcome of the IVF procedure is not correlated with TFPI levels in hFF.

Adult↗

Characterization of calcium oscillation patterns in caprine oocytes induced by IVF or an activation technique used in nuclear transfer.

Routine activation of nuclear transfer (NT) eggs involves the application of a single intracellular calcium [Ca2+]i rise, stimulated by an electrical pulse, as opposed to [Ca2+]i oscillations, which is the natural mode of sperm-induced activation at fertilization in all mammalian species tested to date. It has yet to be shown that caprine oocytes exhibit an increase in calcium at fertilization in a manner similar to other mammals. The objective of the present study was to evaluate and characterize the ([Ca2+]i) oscillation patterns of caprine metaphase II (MII) oocytes during IVF and during an activation techniques used in nuclear transfer. Additionally, the effect of cytochalasin B (cyto B) in the NT process was evaluated for its impact on [Ca2+]i oscillations and subsequent embryo development. Mature in vitro and in vivo derived caprine oocytes were activated by 5 microM ionomycin, an electrical pulse(s), or IVF. The intracellular Ca2+ response was determined using the [Ca2+]i indicator Fura-2 dextran (Fura-2D). Ova treated with ionomycin or stimulated by an electrical pulse exhibited a single [Ca2+]i rise, whereas IVF-derived oocytes showed oscillations. IVF [Ca2+]i showed some variation, with 62% of in vitro matured oocytes exhibiting oscillations, whereas 8% of in vivo matured oocytes exhibited oscillations demonstrating a correlation between [Ca2+]i responses and maturation technique. Knowing the [Ca2+]i profile of activated eggs, one may be able to optimize the activation methodology used in a production nuclear transfer setting which could potentially improve development to term for NT embryos.

Animals↗

Rescue intracytoplasmic sperm injection (ICSI)-salvaging in vitro fertilization (IVF) cycles after total or near-total fertilization failure.

OBJECTIVE: To evaluate the effectiveness of delayed oocyte reinsemination by ICSI (rescue ICSI) after total or near-total fertilization failure (</=25%) in IVF. DESIGN: A retrospective clinical study. SETTING: Non-hospital-based IVF program. PATIENT(S): Thirty IVF cycles with total fertilization failure and two cycles with </=25% initial fertilization. MAIN OUTCOME MEASURE(S): Fertilization and pregnancy rates after rescue ICSI. INTERVENTION(S): Rescue ICSI 19-22 hours after initial oocyte insemination. RESULT(S): A fertilization rate of 60.2% was achieved with rescue ICSI (141 of 234 oocytes, 29 of 32 patients). Of 30 patients with total fertilization failure, 27 had fresh transfers with rescue ICSI embryos. Two additional patients with </=25% initial fertilization had subsequent replacement of frozen-thawed rescue ICSI embryos. Six pregnancies resulted, including three singleton, one twin, one missed abortion, and one ectopic pregnancy (20.7%). One of the singleton pregnancies resulted from replacement of four frozen-thawed embryos and is the first known pregnancy achieved from cryopreserved rescue ICSI embryos. CONCLUSION(S): Rescue ICSI should be considered in the presence of total or near-total fertilization failure in IVF. Early application of rescue ICSI (19-22 hours after insemination) may be critical for establishing fertilization within an optimal window and producing viable embryos and pregnancies.

Adult↗

Subcutaneously administered Repronex in female patients undergoing in vitro fertilization is as effective and well tolerated as intramuscular menotropin treatment. Repronex SC, IVF Study Group.

OBJECTIVE: To determine the efficacy and safety of Repronex SC as compared with Repronex IM and Pergonal IM in patients undergoing IVF. DESIGN: Open-label, randomized, parallel-group, multicenter study. SETTING: Fifteen academic and private fertility clinics with IVF experience. PATIENT(S): Premenopausal women with regular ovulatory menstrual cycles undergoing IVF for infertility attributable to tubal factors, endometriosis (stage I or II), or unknown factors. INTERVENTION(S): Down-regulation with leuprolide acetate followed by up to 12 days of treatments with gonadotropins, hCG administration, oocyte retrieval, and embryo transplant. MAIN OUTCOME MEASURE(S): Mean number of oocytes retrieved, chemical, clinical, and continuing pregnancies, incidence of oocyte retrieval and embryo transfer, and peak serum E2 concentrations. RESULT(S): There were no significant differences among the treatment groups except for a higher percentage of continuing pregnancies in the Repronex SC group. Gonadotropin therapy was well tolerated in all three treatment groups. The Repronex SC group had a significantly higher incidence of transient mild/moderate injection site reactions during the first few days of therapy. CONCLUSION(S): Repronex SC is comparable in therapeutic effectiveness and safety to Repronex IM and Pergonal IM in patients undergoing IVF and provides an alternative route of injection for self-administration of gonadotropin.

Adolescent↗

In vitro fertilization/embryo transfer in the United States: 1987 results from the National IVF-ET Registry.

This is the second annual report of the U.S. Registry of IVF-ET and related practices. The present report describes the 1987 experiences of 96 U.S. member clinics with respect to treatments and outcomes. During 1987, 14,647 in vitro fertilization (IVF) and/or gamete intrafallopian transfer (GIFT) stimulation cycles were performed; there were 490 frozen embryo and 60 donor oocyte transfers. Ninety percent of the clinics had at least one delivery, and overall, a total of 1858 babies were born. The overall clinical pregnancy rates were 16% for IVF (based on 8725 retrievals), 25% for GIFT (based on 1968 retrievals), and 28% for IVF and GIFT in combination (based on 199 retrievals). The results for each procedure are described in detail.

Embryo Transfer↗

Immature oocyte retrieval: lessons from unstimulated IVF cycles.

OBJECTIVE: To describe retrieval of immature oocytes during unstimulated IVF and assess the in vitro maturation and fertilization rates. DESIGN: Retrospective analysis. SETTING: The USC program for assisted reproduction. PATIENT(S): Spontaneously ovulatory women with predominantly pelvic factor as their principal cause of infertility, under the age of 40, and no male factor. INTERVENTION(S): HCG administration in mid-cycle, aspiration of all visible follicles, in vitro maturation of immature oocytes in culture media versus 50% follicular fluid in media, IVF, and embryo transfer. MAIN OUTCOME MEASURE(S): Rates of in vitro maturation, fertilization, and implantation after embryo transfer. RESULT(S): A total of 101 immature oocytes were obtained during 59 follicle aspirations. Thirty percent of prophase I oocytes matured to metaphase II in vitro compared with 44% of metaphase I oocytes. Fertilization rates for matured prophase I oocytes were 62% for those cultured in standard culture media (controls) and 87% for follicular fluid culture media. Two pregnancies resulted from the transfer of embryos derived from immature oocytes when no other embryos were transferred. CONCLUSION(S): Immature oocytes may be retrieved successfully during the mid-cycle aspiration of the dominant follicle in unstimulated IVF cycles. Maturation of immature oocytes in vitro with follicular fluid results in similar maturation and fertilization rates as for control incubation. Immature oocytes thus retrieved contribute to the overall pregnancy success of unstimulated IVF cycles. It may be better to retrieve immature oocytes during unstimulated cycles than during the follicular phase of natural cycles.

Cellular Senescence↗

Diagnostic dilemma encountered when detecting bovine viral diarrhea virus in IVF embryo production.

Routine quality controls in production of bovine embryos by in vitro fertilization (IVF) should include screening all materials of animal origin for the presence of bovine viral diarrhea virus (BVDV). Using a reverse transcription nested polymerase chain reaction (RT-nPCR) assay, we detected BVDV in primary cultures of uterine tubal cells (UTC) that had been used during IVF procedures. The goal of our ensuing investigation was to determine its source and assess risks associated with the identified contaminant. Sequencing of the amplified 5' nontranslated region (NTR) of the viral genome confirmed a Genotype I BVDV contaminant. This viral contaminant was also identified by RT-nPCR in multiple samples of the same lot of fetal bovine serum (FBS) that was used in transport media by the laboratory that harvested the UTC. Both routine and enhanced roller bottle methods for virus isolation failed to detect BVDV in the FBS. Furthermore, virus neutralization assays did identify antibodies to Genotype I strains of BVDV in the FBS. After 7 days of co-incubation, neither cultured, washed UTC nor exposed, washed embryos were RT-nPCR positive for BVDV. Eight embryos produced in the contaminated system were nonsurgically transferred into eight seronegative cows. None of the embryo recipients seroconverted to BVDV. Thus, contamination of cell culture medium with BVDV did not result in transmission of the virus when IVF embryos were transferred. Failure to transmit disease was likely aided by serendipitous control from anti-BVDV antibodies in the FBS. However, a diagnostic dilemma was created when the RT-nPCR assays used to screen for BVDV were positive, yet attempts to isolate the virus were negative. This case study illustrates that if molecular assays are to be used to confirm the pathogen-free status of IVF embryo production systems, media components of animal origin (e.g. FBS) should be screened with molecular assays for BVDV as well as traditional virus isolation techniques.

5' Untranslated Regions↗

Quality controls for bovine viral diarrhea virus-free IVF embryos.

Introduction of bovine viral diarrhea virus (BVDV) with cumulus-oocyte-complexes (COCs) from the abattoir is a concern in the production of bovine embryos in vitro. Further, International Embryo Transfer Society (IETS) guidelines for washing and trypsin treatment of in-vivo-derived bovine embryos ensure freedom from a variety of pathogens, but these procedures appear to be less effective when applied to IVF embryos. In this study, COCs were exposed to virus prior to IVM, IVF and IVC. Then, virus isolations from cumulus cells and washed or trypsin-treated nonfertile and degenerated ova were evaluated as quality controls for IVF embryo production. The effect of BVDV on rates of cleavage and development was also examined. All media were analyzed prior to the study for anti-BVDV antibody. Two approximately equal groups of COCs from abattoir-origin ovaries were washed and incubated for 1 h in minimum essential medium (MEM) with 10% equine serum. One group was incubated in 10(7) cell culture infective doses (50% endpoint) of BVDV for 1 h, while the other was incubated without virus. Subsequently, the groups were processed separately with cumulus cells, which were present throughout IVM, IVF and IVC. Cleavage was evaluated at 4 d and development to morulae and blastocysts at 7 d of IVC. After IVC, groups of nonfertile and degenerated ova or morulae and blastocysts were washed or trypsin-treated, sonicated and assayed for virus. Cumulus cells collected at 4 and 7 d were also assayed for virus. Anti-BVDV antibody was found in serum used in IVM and IVC but not in other media. A total of 1,656 unexposed COCs was used to produce 1,284 cleaved embryos (78%), 960 embryos > or = 5 cells (58%), and 194 morulae and blastocysts (12%). A total of 1,820 virus-exposed COCs was used to produce 1,350 cleaved embryos (74%), 987 embryos > or = 5 cells (54%), and 161 morulae and blastocysts (9%). Rates of cleavage (P = 0.021), cleavage to > or = 5 cells (P = 0.026) and development to morula and blastocyst (P = 0.005) were lower in the virus-exposed group (Chi-square test for heterogeneity). No virus was isolated from any samples from the unexposed group. For the exposed group, virus was always isolated from 4- and 7-d cumulus cells, from all washed nonfertile and degenerated ova (n = 40) and morulae and blastocysts (n = 57) and from all trypsin-treated nonfertile and degenerated ova (n = 80) and morulae and blastocysts (n = 91). Thus, virus persisted in the system despite the presence of neutralizing antibody in IVM and IVC media, and both washing and trypsin treatment were ineffective for removal of the virus. Presence of virus in 4- and 7-d cumulus cells as well as in nonfertile and degenerated ova were good indicators of virus being associated with morulae and blastocysts.

Animals↗

Chromosome analysis of spontaneous abortions after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

OBJECTIVE: To verify the hypothesis that the incidence of chromosomal abnormalities significantly increases in the products of conception of males with sub-fertility, treated with assisted reproduction techniques (ART). STUDY DESIGN: All removed products of conception tissues were analyzed with standard cytogenetic techniques. A karyotype of the abortions was possible in 35 cases of IVF and 29 of ICSI. RESULTS: 15/35 (43%) IVF abortions and 14/29 (48%) ICSI abortions, respectively, have shown a chromosomal abnormality. The most frequent abnormality was monosomy X (45,X0). CONCLUSION: No significant difference in the incidence of embryonic anomalies was found between IVF and ICSI group. However, both IVF and ICSI allow pre-implantation diagnosis and embryo chromosomal evaluation should be considered, before transfer. Genetic counselling and consideration of prenatal diagnosis is suggested as integral part of planning of treatment strategies for 'at risk couples'.

Abortion, Spontaneous↗

[Natural cycle IVF (nIVF) in women with implantation failure].

Since the introduction of IVF treatments, natural cycle IVF (nIVF) has been largely replaced by IVF with ovarian stimulation to obtain multiple oocytes. Failure to anticipate the retrieval of more than two oocytes often results in cancellation of the cycle. However, nIVF has several advantages. It is associated with a close to zero multiple pregnancy rate, and a zero risk of ovarian hyperstimulation syndrome. Per cycle, nIVF is less time consuming, physically and emotionally less demanding for patients, and cheaper than stimulated IVF, but also less effective. GnRH antagonists have improved the outcome of nIVF cycles. They avoid unexpected ovulation and frequent cancellations. In selected cases, especially in women with implantation failure or with poor ovarian response, favorable results can be obtained from nIVF cycles, despite the replacement of a single embryo. Poor results are obtained in women over 38 years.

Abortion, Spontaneous↗

Psychosocial adjustment to unsuccessful IVF and GIFT treatment.

Twenty-one couples for whom in vitro fertilisation (IVF) or GIFT treatment failed were followed-up 15-30 months after treatment and compared with 20 couples for whom IVF had been successful. Current mental health status, quality of life and marital adjustment were assessed via standardised questionnaires. In addition, couples' experiences of IVF/GIFT treatment were explored via a semi-structured interview. Questionnaire results showed that unsuccessful IVF/GIFT recipients cannot be distinguished from general population norms. However, these couples reported more emotional distress relative to those whom treatment had worked and females in particular indicated a lower quality of life. Couples who had at least one child prior to IVF/GIFT treatment tended to show greater emotional distress at follow-up. Both groups gave similar accounts of the positive and negative aspects of IVF/GIFT treatment, but the unsuccessful group felt less supported by the IVF Unit staff and were less satisfied with the counseling they received. The data indicate that post-treatment counseling may be particularly important for facilitating positive reconstructions of the IVF experience when treatment is unsuccessful.

Adaptation, Psychological↗

Optimum number of oocytes for a successful first IVF treatment cycle.

Ovarian stimulation in IVF allows selection of embryos for transfer, but may have detrimental effects on oocyte and embryo quality and endometrial receptivity. This study investigated the optimal response to ovarian stimulation in terms of number of oocytes for achieving pregnancy in a first IVF cycle. Data from 7422 women who underwent their first IVF cycle for standard indications were analysed. All had been treated with exogenous gonadotrophins and gonadotrophin releasing hormone (GnRH) agonist co-treatment in a long down-regulation protocol between 1990 and 1995. Pregnancy rates in relation to the number of obtained oocytes were adjusted for age, fecundity, subfertility cause, gonadotrophin dosage, type of luteal support, and number of transferred embryos by multivariate analysis. Of the 7422 women who underwent oocyte retrieval, overall 85% had an embryo transfer and 24% conceived. The highest pregnancy rates per embryo transfer and per started cycle were observed when 13 oocytes were obtained (31 and 28%, respectively). This study supports the concept of an optimal range of oocytes obtained in response to ovarian stimulation for IVF, below and above which outcomes are compromised.

Adolescent↗