Successful pregnancy with intracytoplasmic sperm injection after bacterial contamination of embryo culture in in vitro fertilization: a case report.

BACKGROUND: Bacterial infection of embryo culture medium is rare but may be detrimental. The main source of embryo culture contamination is semen. Assisted reproduction centers currently lack consensus regarding the methods for preventing and managing embryo culture infection. In our recent case, a successful pregnancy was achieved with intracytoplasmic sperm injection after failed conventional in vitro fertilization owing to bacterial contamination. CASE PRESENTATION: We present a case report of two consecutive in vitro fertilization-intracytoplasmic sperm injection cycles with photo and video documentation of the bacterial growth. A 36-year-old Hungarian woman and her 37-year-old Hungarian partner came to our department. They had two normal births followed by 2 years of infertility. The major causes of infertility were a closed fallopian tube and asthenozoospermia. Bacterial infection of the embryo culture medium was observed during in vitro fertilization and all oocytes degenerated. The source was found to be the semen. To prevent contamination, intracytoplasmic sperm injection was used for fertilization in the subsequent cycle. Intracytoplasmic bacterial proliferation was observed in one of the three fertilized eggs, but two good-quality embryos were successfully obtained. The transfer of one embryo resulted in a successful pregnancy and a healthy newborn was delivered. CONCLUSION: Intracytoplasmic sperm injection may be offered to couples who fail conventional in vitro fertilization treatment owing to bacteriospermia, as it seems to prevent infection of the embryo culture. Even if bacterial contamination appears, our case encourages us to continue treatment. Nevertheless, the development of new management guidelines for the prevention and management of bacterial contamination is essential.

The importance of cytoplasmic strings during early human embryonic development.

Objectives: During human in vitro fertilisation (IVF) treatments, embryologists attempt to select the most viable embryos for embryo transfer (ET). Previously, embryos were evaluated based on light microscopic morphological parameters. However, this is currently accomplished by morphokinetic analysis of time-lapse recordings. This technique provides us the opportunity to observe cytoplasmic strings at the blastocyst stage. The aim of this work was to examine the relationship between the presence of cytoplasmic strings (CS) and the embryo viability in human in vitro fertilised embryos. Study design: Herein, we present an evaluation of the morphokinetic data on the development of embryos obtained during IVF treatments performed at the Division of Assisted Reproduction between December 2020 and March 2021. The dynamics of embryo development, embryo morphology, and morphokinetic scores generated by a time-lapse system were compared between the presence of cytoplasmic strings (CS+) and their absence (CS-) at the blastocyst stage. Results: The development of 208 embryos from 78 patients was examined. Moreover, 81.2% of the embryos had CS in the blastocyst stage; 77% of CS existed in embryos created by conventional IVF, while 86% of CS existed in embryos fertilised by intracytoplasmic sperm injection (ICSI) (p = 0.08). A greater number of CS+ embryos developed into a higher quality blastocyst (52.1% vs. 20.5%, p = 0.02). The morphokinetic score values characterising the development of embryos, such as Known Implantation Data Score (KIDScore) and Intelligent Data Analysis (iDAScore), were higher in CS+ groups (KID: 6.1 ± 2.1 vs. 4.7 ± 2.07; iDA: 8.0 ± 1.9 vs. 6.8 ± 2.3, p < 0.01). The dynamics of the early embryo development were similar between the two groups; however, CS+ embryos reached the blastocyst stage significantly earlier (tB: 103.9 h vs. tB: 107.6 h; p = 0.001). Conclusion: Based on our results, the number of embryos with cytoplasmic strings was higher than that without cytoplasmic strings, and its presence is not related to the fertilisation method. These embryos reached the blastocyst stage earlier, and their morphokinetic (KIDScore and iDAScore) parameters were better. All these results suggest that the presence of CS indicates higher embryo viability. The examination of this feature may help us make decisions about the embryos with higher implantation potential.

Intracytoplasmic sperm injection does not improve the outcome of IVF treatments in patients with advanced maternal age or low oocyte number: A randomized controlled trial.

INTRODUCTION: Intracytoplasmic sperm injection (ICSI) was introduced to achieve fertilization in cases of severe male factor infertility. However, ICSI is often used in cases of non-male factor infertility, such as advanced maternal age or low oocyte number, but the clinical benefit of the method in these indications has not been proven. MATERIAL AND METHODS: A prospective randomized study was conducted in a university clinic between 2018 and 2020. Patients with ≥40 years of age and/or ≤4 oocytes with non-sever male factor infertility were randomized into conventional IVF or ICSI groups. Fertilization rate, embryo quality, implantation, clinical pregnancy and live birth rates were compared. RESULTS: A total of 336 IVF cycles (169 conventional IVF and 167 ICSI) were involved in the study. The fertilization rate was higher in the conventional IVF group compared to the ICSI group (IVF: 61.7%, ICSI: 53.4%, P=0.001). Embryo development and morphology did not show considerable difference between groups. Implantation, clinical pregnancy and live birth rate were 13.1%, 24.3% and 11.4% in the conventional IVF and 10.4%, 19.0%, 12.0% in the ICSI group. The differences were not significant. Subgroup analysis showed a significantly better clinical outcome following conventional IVF when advanced maternal age was accompanied by low oocyte number (Implantation: 11.7% vs 2.6%, P=0.027; Clinical pregnancy: 18.5% vs 4%, P=0.020). DISCUSSION: A significantly higher fertilization rate, a tendency for higher clinical pregnancy rate was found in conventional IVF treatments compared to ICSI. When advanced maternal age was associated with low oocyte number, ICSI resulted in a substantially lower chance of fertilization and clinical pregnancy. These data suggest that ICSI offers no advantage over conventional IVF in terms of fertilization, embryo quality, implantation and pregnancy rates for couples with advanced maternal age or with low oocyte number.

[Is bacteriological screening of semen samples before in vitro fertilization treatment justified?] / Indokolt-e a spermaminták bakteriológiai szurése in vitro fertilizáció elott?

The number of couples seeking assisted reproductive technologies is increasing worldwide. The question of whether routine bacteriological screening of semen is necessary during the investigation and treatment of infertility is controversial. The semen sample often contains bacteria even if the hygiene rules for collection are followed. There is a growing number of studies dealing with the importance of the semen microbiome. Bacteriospermia can result not only from infection but also from contamination or colonization. Symptomatic infections or sexually transmitted diseases should be treated, but the relevance of asymptomatic positive cultures is controversial. Several studies have suggested that urinary tract infections may play a role in male infertility and that the quality of semen may be impaired by elevated bacterial or white blood cell counts. However, there are conflicting results on the effect of the treatment of bacteriospermia and leukocytospermia on sperm quality. Semen contaminated with microbes may also infect the embryos, thus compromising the success of treatment. In contrast, most studies have found no significant difference in the effectiveness of in vitro fertilization treatment in the presence or absence of bacteriospermia. This can be explained by the sperm preparation techniques, the antibiotic content of the culture media and the use of the intracytoplasmatic sperm injection technique. Thus, the need for routine semen culture before in vitro fertilization treatment and the management of asymptomatic bacteriospermia is questionable. Orv Hetil. 2023; 164(17): 660-666.

Prospective-randomized study comparing clinical outcomes of IVF treatments where embryos were cultured individually or in a microwell group culture dish.

Culturing embryos together in a microdrop of media may improve embryo quality, based on the results of animal studies, however individual identification of the embryos in such a system is not possible. The microwell group culture dish contains 9 or 16 microwells with a minimal well-to-well distance and a specific well morphology that facilitates paracrine and autocrine effects. The microwell group culture dish enables individual identification of the embryos while providing the environment that comes with similar benefits as group culture. Our aim was to investigate whether embryo culture in the microwell group culture dish (Primo Vision Dish, Vitrolife) improves IVF outcomes compared to individual culture in human IVF treatment. Five hundred thirty-two IVF-ET cycles were enrolled in this prospective randomized study in a university hospital. IVF cycles were randomized into microwell group culture and individual culture groups. Primary outcome measure was clinical pregnancy rate and secondary outcome measures were embryo quality, fertilization, implantation, delivery and embryo utilization rates. Fertilization rate in ICSI cycles was significantly higher in the microwell group culture group (70.6% vs. 64.9%, P = 0.001). Clinical pregnancy rate was 50.8% in the group culture and 40.6% in the individual culture (P = 0.022). Live birth rate was 41.5% in microwell and 32.9% in individual culture (P = 0.0496). Embryo utilization rate was higher in microwell group culture than in individual culture (80.6% vs. 75.0%; P < 0.001). Microwell group culture has a beneficial effect on IVF outcome and it also allows following up individual embryo development.ClinicalTrials.gov: NCT01774006.

ESHRE guideline: ovarian stimulation for IVF/ICSI†.

STUDY QUESTION: What is the recommended management of ovarian stimulation, based on the best available evidence in the literature? SUMMARY ANSWER: The guideline development group formulated 84 recommendations answering 18 key questions on ovarian stimulation. WHAT IS KNOWN ALREADY: Ovarian stimulation for IVF/ICSI has been discussed briefly in the National Institute for Health and Care Excellence guideline on fertility problems, and the Royal Australian and New Zealand College of Obstetricians and Gynaecologist has published a statement on ovarian stimulation in assisted reproduction. There are, to our knowledge, no evidence-based guidelines dedicated to the process of ovarian stimulation. STUDY DESIGN SIZE DURATION: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 8 November 2018 and written in English were included. The critical outcomes for this guideline were efficacy in terms of cumulative live birth rate per started cycle or live birth rate per started cycle, as well as safety in terms of the rate of occurrence of moderate and/or severe ovarian hyperstimulation syndrome (OHSS). PARTICIPANTS/MATERIALS SETTING METHODS: Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 84 recommendations: 7 recommendations on pre-stimulation management, 40 recommendations on LH suppression and gonadotrophin stimulation, 11 recommendations on monitoring during ovarian stimulation, 18 recommendations on triggering of final oocyte maturation and luteal support and 8 recommendations on the prevention of OHSS. These include 61 evidence-based recommendations-of which only 21 were formulated as strong recommendations-and 19 good practice points and 4 research-only recommendations. The guideline includes a strong recommendation for the use of either antral follicle count or anti-Müllerian hormone (instead of other ovarian reserve tests) to predict high and poor response to ovarian stimulation. The guideline also includes a strong recommendation for the use of the GnRH antagonist protocol over the GnRH agonist protocols in the general IVF/ICSI population, based on the comparable efficacy and higher safety. For predicted poor responders, GnRH antagonists and GnRH agonists are equally recommended. With regards to hormone pre-treatment and other adjuvant treatments (metformin, growth hormone (GH), testosterone, dehydroepiandrosterone, aspirin and sildenafil), the guideline group concluded that none are recommended for increasing efficacy or safety. LIMITATIONS REASON FOR CAUTION: Several newer interventions are not well studied yet. For most of these interventions, a recommendation against the intervention or a research-only recommendation was formulated based on insufficient evidence. Future studies may require these recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in ovarian stimulation, based on the best evidence available. In addition, a list of research recommendations is provided to promote further studies in ovarian stimulation. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. F.B. reports research grant from Ferring and consulting fees from Merck, Ferring, Gedeon Richter and speaker's fees from Merck. N.P. reports research grants from Ferring, MSD, Roche Diagnositics, Theramex and Besins Healthcare; consulting fees from MSD, Ferring and IBSA; and speaker's fees from Ferring, MSD, Merck Serono, IBSA, Theramex, Besins Healthcare, Gedeon Richter and Roche Diagnostics. A.L.M reports research grants from Ferring, MSD, IBSA, Merck Serono, Gedeon Richter and TEVA and consulting fees from Roche, Beckman-Coulter. G.G. reports consulting fees from MSD, Ferring, Merck Serono, IBSA, Finox, Theramex, Gedeon-Richter, Glycotope, Abbott, Vitrolife, Biosilu, ReprodWissen, Obseva and PregLem and speaker's fees from MSD, Ferring, Merck Serono, IBSA, Finox, TEVA, Gedeon Richter, Glycotope, Abbott, Vitrolife and Biosilu. E.B. reports research grants from Gedeon Richter; consulting and speaker's fees from MSD, Ferring, Abbot, Gedeon Richter, Merck Serono, Roche Diagnostics and IBSA; and ownership interest from IVI-RMS Valencia. P.H. reports research grants from Gedeon Richter, Merck, IBSA and Ferring and speaker's fees from MSD, IBSA, Merck and Gedeon Richter. J.U. reports speaker's fees from IBSA and Ferring. N.M. reports research grants from MSD, Merck and IBSA; consulting fees from MSD, Merck, IBSA and Ferring and speaker's fees from MSD, Merck, IBSA, Gedeon Richter and Theramex. M.G. reports speaker's fees from Merck Serono, Ferring, Gedeon Richter and MSD. S.K.S. reports speaker's fees from Merck, MSD, Ferring and Pharmasure. E.K. reports speaker's fees from Merck Serono, Angellini Pharma and MSD. M.K. reports speaker's fees from Ferring. T.T. reports speaker's fees from Merck, MSD and MLD. The other authors report no conflicts of interest. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.) †ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.

Erratum: ESHRE guideline: ovarian stimulation for IVF/ICSI.

[This corrects the article DOI: 10.1093/hropen/hoaa009.][This corrects the article DOI: 10.1093/hropen/hoaa009.].

[Pathophysiology and current clinical approach of ovarian hyperstimulation syndrome]. / Az ovarialis hiperstimulációs szindróma kórélettana és korszeru klinikuma.

During assisted reproduction technologies, controlled hyperstimulation of the ovaries occurs. Ovarian hyperstimulation syndrome is an excessive overreaction of the ovaries complicating pharmacological ovulation induction. Rarely other causes, such as the mutation of the follicle-stimulating hormone receptor may also be in the background. Ovarian hyperstimulation syndrome is clinically characterized by a massive ovarian enlargement associated with an acute third-space fluid shift responsible for the development of ascites, and sometimes pleural or pericardial effusion. Associated arterial or venous thromboembolic symptoms are also common. Ovarian hyperstimulation syndrome is an iatrogenic and potentially life-threatening condition in the form of ischemic stroke or circulatory insufficiency of the limbs. Recently some new methods have been developed for the prevention of the disease. The syndrome affects young, healthy patients. It also has an important economic burden due to the absence from work, bed rest, or hospitalization and intensive medical management of more severe cases. Supportive therapy, anticoagulant prophylaxis and close monitoring are the main approach for the syndrome. However, hospitalization or intervention should not be delayed for patients with severe or critical conditions. Orv Hetil. 2018; 159(34): 1390-1398.

A randomized controlled trial comparing the efficacy and safety of two HMG preparations gaining their LH bioactivity from different HCG sources.

In this prospective, controlled, randomized, multicentre, non-inferiority study, efficacy and safety of two HMG preparations (Menopur®- Ferring and Meriofert®- IBSA Institut Biochimique SA) for ovarian stimulation were compared (270 women undergoing IVF aged between 18 and 39 years; BMI 30 kg/m2 or less; less than three prior completed assisted reproduction technique cycles). A standard long down-regulation with gonadotrophin-releasing hormone agonist protocol, with HCG triggering was used; primary end-point was total number of oocytes retrieved; attention was paid toovarian hyperstimulation syndrome (OHSS). No statistically significant differences between the treatment groups were reported for most of the clinically significant end-points, including embryo quality, fertilization rate, implantation rate, ongoing pregnancy rate and live birth rate. Total number of oocytes retrieved was higher in the new HMG group compared with the reference (11.6 ± 6.6 and 9.7 ± 5.9, respectively, with a 95% CI of the difference equal +0.43 to +3.43). Increased number of oocytes was obtained through a shorter stimulation, but HMG units per oocyte retrieved were equivalent. The safety profile of the products for frequency of ovarian hyperstimulation syndrome was the same. This study showed that the new HMG preparation is a viable alternative for conducting ovarian stimulation in IVF cycles.

Embryo density may affect embryo quality during in vitro culture in a microwell group culture dish.

PURPOSE: Culturing embryos in groups is a common practice in mammalian embryology. Since the introduction of different microwell dishes, it is possible to identify oocytes or embryos individually. As embryo density (embryo-to-volume ratio) may affect the development and viability of the embryos, the purpose of this study was to assess the effect of different embryo densities on embryo quality. METHODS: Data of 1337 embryos from 228 in vitro fertilization treatment cycles were retrospectively analyzed. Embryos were cultured in a 25 µl microdrop in a microwell group culture dish containing 9 microwells. Three density groups were defined: Group 1 with 2-4 (6.3-12.5 µl/embryo), Group 2 with 5-6 (4.2-5.0 µl/embryo), and Group 3 with 7-9 (2.8-3.6 µl/embryo) embryos. RESULTS: Proportion of good quality embryos was higher in Group 2 on both days (D2: 18.9 vs. 31.5 vs. 24.7%; p < 0.001; D3: 19.7 vs. 27.1 vs. 21.2%; p = 0.029; Group 1. vs. Group 2. vs. Group 3). Cell number on Day 3 differed between Groups 1 and 2 (6.8 ± 2.2; 7.3 ± 2.1; p = 0.004) and Groups 2 and 3 (7.3 ± 2.1 vs. 7.0 ± 2.0; p = 0.014). CONCLUSIONS: Culturing 5-6 embryos together in a culture volume of 25 µl may benefit embryo quality. As low egg number, position, and distance of the embryos may influence embryo quality, results should be interpreted with caution.

Assessment of the immunogenicity of gonadotrophins during controlled ovarian stimulation.

PROBLEM: Gonadotrophin hormones are used for the controlled ovarian stimulation (COS) as part of the in vitro fertilization techniques. Therapeutic proteins have the potential to induce an unwanted immune response. METHOD OF STUDY: The presence of anti-FSH, anti-LH and anti-hCG antibodies were determined in patients from two different clinical trials after the repeated administration of hMG or FSH. RESULTS: In the first study, 27 subjects were screening for the presence of anti-FSH antibodies. From the 27 patients, only one patient showed the presence of low levels of antibodies. In a second study, 25 patients were screened for the presence of anti-FSH, anti-LH and anti-hCG antibodies. At the end of the study, no patients showed the presence of antibodies. CONCLUSION: The results of this study suggest that repeated treatment cycles with FSH or hMG in patients undergoing COS for in vitro fertilization can be safely and effectively applied without concerns for immunogenicity.

[First attempts in the introduction of cryopreservation of ovarian tissues]. / Kezdeti tapasztalataink a petefészekszövet-fagyasztás bevezetésével.

INTRODUCTION: The oncological treatment may damage ovarian function. To prevent this, it is possible to cryopreserve the ovarian tissue, and to keep the samples for long-term storage. The frozen-thawed tissue could be retransplanted after chemo- or radiotherapy. AIM: The aim of our study was to examine the effect of cryopreservation on the viability of ovarian tissue. METHOD: We analyzed the survival of frozen-thawed donated ovarian tissues. The quality of the follicles and hormone production in fresh and frozen-thawed samples were compared. RESULTS: Histological analysis showed that the number of viable follicles was reduced by 23% in the frozen-thawed samples. However, viable follicles still presented in post thawing ovarian tissues. Maximal estradiol production in frozen-thawed tissues was 908 pg/ml and hormone production was similar to the control tissues. The maximal progesterone production was 1.95 ng/ml post thawing, but these values were lower than the progesterone production of fresh tissues. CONCLUSIONS: The method of ovarian cryopreservation used in our laboratory was able preserve the viability of follicles in frozen-thawed ovarian tissues. Orv. Hetil., 2016, 157(49), 1947-1954.

Giant oocytes in human in vitro fertilization treatments.

PURPOSE: Giant oocytes are potential sources of chromosomal abnormalities and should thus never be used in in vitro fertilization and embryo transfer (IVF-ET) procedures. The presence of giant oocytes may indicate the efficiency of the ovarian stimulation and can refer to the quality of sibling oocytes. METHODS: IVF cycles performed between January 2008 and November 2013 (n = 1521) were divided into two groups: Giant Oocyte Group (GO Group) contained cycles with at least one giant oocyte in the cohort of the retrieved oocytes (n = 37), Normal Group contained cycles with no giant oocytes (n = 1484). In the second part of the study, cycles from GO Group and Normal Group were matched according to patient age, number of retrieved oocytes and stimulation protocol, and thus 30 pairs were formed. Clinical and embryological data were analyzed. RESULTS: The incidence of giant oocytes was 0.3 %. The average patient age was lower (33.5 ± 3.9 vs. 35.3 ± 4.9, p = 0.02); estradiol (E2) levels (1954 ± 903 vs. 1488 ± 909 pg/l, p < 0.01) and number of retrieved oocytes (12.7 ± vs 8.1 ± 5.1, p < 0.01) were significantly higher in the GO Group. There was no difference in clinical pregnancy rates (37.8 vs. 37.4 %, p = 1.00) between the two groups. No major differences in the embryo qualities were found. In the second part of the study, fertilization rate in the matched GO Group was lower (50.6 ± 21.9 vs. 61.9 ± 22.4 %, p = 0.04). Clinical pregnancy rates (36.7 vs. 36.7 %, p = 1.00) did not differ between the matched cycles. CONCLUSIONS: Our data suggest that the stimulation protocol does not affect the incidence of giant oocytes. Giant oocytes present in cycles with higher number of retrieved oocytes in younger women. The presence of these gametes does not refer to the quality of sibling oocytes and embryos, or the outcome of the treatment.

Effect of hyaluronan-enriched embryo transfer medium on IVF outcome: a prospective randomized clinical trial.

PURPOSE: This prospective randomized study reports the effect of hyaluronan-enriched embryo transfer media on the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatments. METHODS: A total of 581 IVF-ET cycles were included in this study. In the Hyaluronan (HA) group (n = 290), embryos were transferred from hyaluronan-enriched transfer medium. In Control group (n = 291), a conventional embryo transfer medium was used. RESULTS: There was no significant difference in clinical pregnancy rate (42.4 vs. 39.2%), implantation rate (23.3 vs. 23.2%), and delivery rate (31.0 vs. 29.2%) between the HA group and the Control group. The number of newborns was also similar in the two groups (111 vs. 110). However, birth weight was significantly higher in the HA group than in the Control group (3,018 ± 598 g vs. 2,724 ± 698 g, P = 0.001). Clinical pregnancy, implantation and delivery rates did not differ significantly between the HA and the Control group when cycles with advanced maternal age, previous IVF failures, low oocyte number or poor embryo quality were compared. CONCLUSION: Our results suggest that hyaluronan enrichment of the embryo transfer media does not seem to have any beneficial effect on IVF outcome. However, further study is needed to clarify the role of hyaluronan in the implantation process and on the birth weight.

Human oocytes containing large cytoplasmic vacuoles can result in pregnancy and viable offspring.

The effect of oocyte dysmorphism on further embryo development is controversial. It is generally accepted that serious oocyte abnormalities can have a negative effect on further fertilization and development. A couple reported to the clinic following 2 years of infertility and underwent five IVF/intracytoplasmic sperm injection treatments due to severe male factor infertility. A total of 42 oocytes were collected. The majority of the oocytes showed at least one large, fluid-filled and centrally located cytoplasmic vacuole and unusually thin zona pellucida. Only seven oocytes showed normal fertilization. The first four IVF treatments did not result in pregnancy. In the fifth IVF treatment, three poor-quality vacuolized embryos were transferred. A singleton pregnancy was detected. A baby girl was born at term who required surgery because of a double left kidney and ureter. This case report demonstrates that serious oocyte abnormalities can be a recurrent phenomenon in the same patient. However, the presence of a large vacuole does not completely block the fertilization process and this abnormal cohort of oocytes can still result in normal embryo development and a viable offspring. Rigorous prenatal care and follow-up should be carried out following the transfer of embryos developed from dysmorphic oocytes.

Factors affecting success rates in two concurrent clinical IVF trials: an examination of potential explanations for the difference in pregnancy rates between the United States and Europe.

OBJECTIVE: To compare a US clinical trial of gonadotropin therapy for IVF with a similar European trial to determine what factors may explain the higher clinical pregnancy rate in the US trial. DESIGN: Comparison of baseline, treatment, and outcome variables in the United States (US) and European trials. SETTING: IVF practices in the US (n=4) and Europe (n=6). PATIENT(S): 297 women undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Clinical pregnancy rates were 43.4% in the US compared with 29.7% in Europe (p=0.016), with a live birth rate of 38.2% versus 27.6% (p=0.064). This difference in clinical pregnancy rate could not be explained by differences in the US versus Europe for number of embryos transferred (2.3 vs. 2.6) or female age (34.6 vs. 30.4). Although the starting dose of gonadotropin was higher in the US trial compared with the European trial (300 versus 225 IU), the total dose of gonadotropin was only slightly higher in the US. In multiple logistic regression analysis of 81 pretransfer variables on clinical pregnancy, the only two found to be significant predictors of outcome were baseline endometrial thickness following down-regulation and number of days of gonadotropin treatment. CONCLUSION(S): This study suggests the possibility that US pregnancy rates may be higher in part because of differences in down-regulation or gonadotropin dosing. Other factors not assessed in these studies or in national datasets likely also contribute to the difference in pregnancy rates.

Impact of GnRH analogues on oocyte/embryo quality and embryo development in in vitro fertilization/intracytoplasmic sperm injection cycles: a case control study.

BACKGROUND: Despite the clinical outcomes of ovarian stimulation with either GnRH-agonist or GnRH-antagonist analogues for in vitro fertilization (IVF) being well analysed, the effect of analogues on oocyte/embryo quality and embryo development is still not known in detail. The aim of this case-control study was to compare the efficacy of a multiple-dose GnRH antagonist protocol with that of the GnRH agonist long protocol with a view to oocyte and embryo quality, embryo development and IVF treatment outcome. METHODS: Between October 2001 and December 2008, 100 patients were stimulated with human menopausal gonadotrophin (HMG) and GnRH antagonist in their first treatment cycle for IVF or intracytoplasmic sperm injection (ICSI). One hundred combined GnRH agonist + HMG (long protocol) cycles were matched to the GnRH antagonist + HMG cycles by age, BMI, baseline FSH levels and by cause of infertility. We determined the number and quality of retrieved oocytes, the rate of early-cleavage embryos, the morphology and development of embryos, as well as clinical pregnancy rates. Statistical analysis was performed using Wilcoxon's matched pairs rank sum test and McNemar's chi-square test. P < 0.05 was considered statistically significant. RESULTS: The rate of cytoplasmic abnormalities in retrieved oocytes was significantly higher with the use of GnRH antagonist than in GnRH agonist cycles (62.1% vs. 49.9%; P < 0.01). We observed lower rate of zygotes showing normal pronuclear morphology (49.3% vs. 58.0%; P < 0.01), and higher cell-number of preembryos on day 2 after fertilization (4.28 vs. 4.03; P < 0.01) with the use of GnRH antagonist analogues. The rate of mature oocytes, rate of presence of multinucleated blastomers, amount of fragmentation in embryos and rate of early-cleaved embryos was similar in the two groups. Clinical pregnancy rate per embryo transfer was lower in the antagonist group than in the agonist group (30.8% vs. 40.4%) although this difference did not reach statistical significance (P = 0.17). CONCLUSION: Antagonist seemed to influence favourably some parameters of early embryo development dynamics, while other morphological parameters seemed not to be altered according to GnRH analogue used for ovarian stimulation in IVF cycles.

Factors affecting reproductive outcome following abdominal myomectomy.

PURPOSE: Fibroids may cause infertility and recurrent pregnancy loss. Studies have analysed the reproductive results after myomectomy according to the size, location and number of fibroids removed, but data are insufficient about comparison of opening the uterine cavity or not during surgery. MATERIALS AND METHODS: Two hundred twenty-nine abdominal myomectomies with the indication of infertility and/or recurrent pregnancy loss were analysed retrospectively. The main purpose was to compare postoperative pregnancy, delivery and miscarriage rates according to either the uterine cavity was opened or not during the surgery. As a secondary outcome postoperative pregnancy rates were assessed by location, size and number of fibroids. RESULTS: There was no significant difference in reproductive results according to either the uterine cavity was opened or remained closed. Preoperative location, size and number of fibroids did not influence significantly the postoperative pregnancy rates. CONCLUSION: Opening the uterine cavity does not impair postoperative pregnancy rates. Preoperative location, size and number of fibroids do not influence postoperative reproductive results.

[Use of biochemical markers to predict the outcome of pregnancies conceived by in vitro fertilization]. / In vitro fertilizáció utján fogant terhességek kimenetelének elorejelzése biokémiai markerekkel.

BACKGROUND: Pregnancies obtained after in vitro fertilization and embryo transfer are at increased risk for an adverse outcome compared with women who conceive naturally. Multiple gestations also occur more frequently after in vitro fertilization. Therefore, there is a need for markers that accurately detect the establishment of pregnancy and predict its outcome as early as possible, allowing for modification of monitoring and treatment if required. Ultrasound examination is part of the routine follow-up after in vitro fertilization, but a gestational sac is not reliably visible until 33-37 days after ovulation induction. As a result, there is an ongoing effort to find endocrine markers that can earlier detect the establishment of pregnancy and forecast its outcome. OBJECTIVE: The authors' aim was to assess the predictive value of the following potential serum markers, measured in the second week after embryo transfer in samples collected prospectively during the past ten years at the Division of Assisted Reproduction of their department: total beta-hCG (theoretical post-embryo transfer day 11 values, calculated from levels in two samples collected with a difference of two days, based on the mathematical model describing its exponential increase in early pregnancy), inhibin A, and CA-125. METHODS: Data of patients undergoing IVF or intracytoplasmic sperm injection and embryo transfer between 1995 and 2001 were analyzed. Establishment of pregnancy was assessed by measuring total beta-hCG concentrations in two serum samples collected between 8 and 16 days after ET with a difference of two days. Measurement of inhibin A and CA-125 levels was performed in the same samples. Logistic regression analyses were used to study the association of these serum markers and the number of retrieved oocytes and transferred embryos with pregnancy outcome. Receiver-operating characteristic (ROC) curves were constructed to identify optimal cutoff levels for outcomes and to assess overall predictive accuracy. RESULTS AND CONCLUSIONS: (1) Day 11 total beta-hCG can be used to compare hCG levels in samples from different sampling days and to predict early pregnancy losses and multiple ongoing pregnancies with high sensitivity and specificity. (2) Inhibin A concentrations are more accurate than day 11 hCG levels for predicting preclinical abortion after IVF but they have no advantage in forecasting ongoing or multiple ongoing pregnancies. (3) Prognostic accuracy of CA-125 measurements for the prediction of pregnancy as well as its outcome is inferior to that achieved with inhibin A.

Reproductive performance after transabdominal metroplasty: a review of 157 consecutive cases.

OBJECTIVE: To evaluate the impact of conventional transabdominal metroplasty on the reproductive outcome of symmetric uterine anomalies and to determine the complications of this procedure. STUDY DESIGN: A retrospective clinical analysis of 157 consecutive women who underwent surgery during a 25-year period. One hundred fifty-seven patients with a subseptate, septate or bicornuate uterus and history of recurrent abortions (124 cases) or infertility (33 cases) were included in this study. Operative technique was similar to the procedure first described by Bret and Guillet and by Tompkins. RESULTS: The fetal survival rate increased from 0.0% before surgery to 81.9% postoperatively in the recurrent abortion group and to 92.8% in the infertility group. Among women having undergone surgery, 63.8% gave birth to at least 1 healthy child, the proportion of previous habitually miscarrying and infertile women was 70.2% and 32.0%, respectively. No uterine rupture or any other complication was observed. CONCLUSION: Conventional transabdominal metroplasty seems to be a safe procedure in women with symmetric uterine anomalies and a history of recurrent miscarriages or otherwise unexplained primary infertility. No perioperative or subsequent peripartum complications were observed. Even in the era of operative hysteroscopy, transabdominal metroplasty remains the only approach in cases of bicornuate uterus.