IVF Success Rates Research Articles

Mitochondrial membrane potential disruption pattern in human sperm

Loss of mitochondrial membrane potential (DeltaPsi(m)) in spermatozoa is correlated with high levels of reactive oxygen species in semen, abnormal spermiogram parameters, and low success rates of IVF. In somatic cells, the loss of DeltaPsi(m) is primarily associated with several mechanisms of cell death, mainly the activation of caspases. The impact of mitochondrial dysfunction on sperm function is still not fully elucidated, although disruption of DeltaPsi(m) and activation of caspases are processes thoroughly studied in human ejaculates. Disruption of DeltaPsi(m) in sperm can be externally triggered by the antineoplastic agent betulinic acid (BA). In this study, we determined whether caspase activation is necessary for the BA-induced disruption of DeltaPsi(m) in human sperm. Viable and highly motile sperm cells were selected through a swim-up process and incubated with 90 microg/ml BA. To elucidate the caspase dependency of BA-triggered disruption of DeltaPsi(m), we used the pan-caspase inhibitor zVAD-fmk and the caspase-3/7 inhibitor DEVD-cho. Exposing highly motile sperm to BA caused a specific disruption of DeltaPsi(m) (P < 0.001 versus control) and a corresponding increase in caspase-3/7 activity (P < 0.001 versus control). Pre-incubation of the sperm with zVAD-fmk or DEVD-cho only partially inhibited BA-induced loss of DeltaPsi(m) (P < 0.05 versus control). We found that caspases directly participate in the loss of DeltaPsi(m) caused by BA in human sperm cells. However, caspase-independent pathways may also be present.

Life after unsuccessful IVF treatment in an assisted reproduction unit: a qualitative analysis of gains through loss among Chinese persons in Hong Kong

Previous studies examining experiences of infertility focused mainly on the aspect of loss but neglected the possible gains realized through surviving the experience of infertility. The success rate of IVF remains relatively low, and we used the strengths perspective to examine adjustment after unsuccessful treatment. This study aims to provide an in-depth description of the gains perceived by Chinese men and women and how they re-constructed their lives after unsuccessful IVF treatment. Four couples and another six women who experienced unsuccessful IVF treatment were recruited from an assisted reproduction clinic. Data were collected through in-depth interviews, using a grounded theory constructivist approach. Of the 10 women and 4 men interviewed, 9 remained childless, 3 had adopted a child and 2 had conceived naturally. They reported gains on a personal level, interpersonal level and transpersonal level through surviving the experience of infertility. All, regardless of the eventual outcome, reported at least one form of personal gain: in personality or knowledge gain. Interpersonal gains were perceived in relationships with their spouses, children, parents, friends, colleagues and fellow IVF service users. More than half of them reported spiritual growth and a change in identity through integrating their experiences and offering help to others. Despite the small sample size, this study makes a significant contribution by suggesting that while negative feelings provoked by the failure to conceive should be acknowledged, people in this situation should also be enabled to consolidate their negative experiences of IVF constructively, helping them to move on with their lives.

Optimal dose of HCG for final oocyte maturation in IVF cycles: absence of evidence?

There is an ongoing debate over the optimal dose of urinary HCG (u-HCG) that can trigger final oocyte maturation, leading to higher IVF success rate without increasing the risk of ovarian hyperstimulation syndrome (OHSS). A systematic review was conducted of all studies that compared the effect of at least two doses of u-HCG for final oocyte maturation on IVF outcomes and on the incidence of OHSS. The primary outcome was the live birth rate, and the secondary end-points were the number of oocytes retrieved, fertilization, implantation and pregnancy rates, and the incidence of OHSS. Only two amongst the six included studies were randomized controlled trials (RCT). Meta-analytic pool was not feasible due to insufficient number of studies assessing the same outcome and significant heterogeneity. The majority of studies concluded that the clinical outcomes were similar between women receiving 5000 or 10,000 IU of u-HCG. The incidence of OHSS was not reduced in the high-risk population even with lower dose of u-HCG. Until large scale RCT addressing the clinical effectiveness and the adverse outcomes related to various doses of u-HCG are conducted, the dose of u-HCG for final oocyte maturation for women referred for IVF needs to be individualized.

Does FSH at the time of hCG trigger improve IVF outcomes? A double blind randomized control trial

OBJECTIVE: Over the past two decades, improvements in IVF success rates have been largely due to improvements in embryo culture and laboratory conditions, while less investigation has been directed toward methods of hCG induction of final oocyte maturation. Normal ovulation is preceded by a surge in both LH and FSH. We hypothesize that FSH, concurrent with the LH surge, may play a positive role in oocyte maturation and developmental competence. Presented is a randomized controlled trial to evaluate reproductive outcomes of FSH versus placebo at the time of hCG trigger. DESIGN: Double blind randomized control clinical trial (RCT), interim analysis. MATERIALS AND METHODS: During a long agonist suppression protocol subjects were randomized by sealed envelope allocation to an FSH bolus (6 amps) vs. placebo at the time of hCG trigger. Clinical and laboratory characteristics were recorded and serum and follicular fluid hormone levels were measured. Clinical pregnancy was defined by fetal heart motion at time of ultrasound. Data will be analyzed using Student t-tests and Chi-square as appropriate on an intention to treat basis. RESULTS: To date, 69 subjects have completed cycles after randomization (Table 1). Seven were excluded for either serum estradiol level at time of trigger >4500pg/mL, or failure to use study drug. There were no significant differences in this interim analysis between the two arms for any baseline covariates.Tabled 1FSH n=35Placebo n=34Age34.8 +/- 3.435.3 +/- 3.8Peak Estradiol (pg/mL)2562 +/- 10572529 +/- 980Mean Number of Oocytes Recovered15.7 +/- 10.314.2 +/- 7.5ICSI Fertilization (2PN/MII)79.2% n=2969.6% n=29IVF Fertilization (2PN/Egg recovered)63.8% n=355.4% n=5Number of Embryos Transferred2.1 +/- 1.12.5 +/- 1.2Clinical Pregnancy Rate60.0%47.1%Ongoing Pregnancy Rate45.7%38.2% Open table in a new tab CONCLUSIONS: These preliminary data, to determine the impact of an FSH bolus at the time of hCG trigger on IVF outcomes, indicate a trend toward improved fertilization and pregnancy rates. Data collection is ongoing and final data analysis on oocyte recovery, fertilization rates, embryo quality and pregnancy outcome will be presented.

Total failed fertilization in IVF: current etiologies and predictors

OBJECTIVE: While improvement of assisted reproductive technologies including ICSI has greatly increased IVF success rates, total fertilization failure remains a devastating cause of failed IVF. By examining cases of total fertilization failure we sought to 1) establish the current etiologies of IVF fertilization failure and 2) identify predictors of fertilization failure to better guide management and counseling of patients.

A decision analysis of treatments for nonobstructive azoospermia associated with varicocele

To examine the economic impact of initial treatments for varicocele-associated nonobstructive azoospermia, specifically varicocelectomy versus microsurgical testicular sperm extraction (TESE) with IVF/intracytoplasmic sperm injection (ICSI). Decision analytic model based on 1) outcomes data from Society for Assisted Reproductive Technology (SART) database and peer-reviewed literature and 2) costing data from Medicare Resource-Based Relative Value Scale and sampling of high volume US IVF centers. Academic medical center. Simulation with a decision analytic model. Variation of successful spontaneous live delivery after varicocelectomy versus rate of successful live delivery after IVF/ICSI. Cost-effectiveness. Microsurgical TESE was more cost effective than varicocelectomy. In 1999, initial treatment with microsurgical TESE was more cost effective ($65,515) than varicocelectomy ($76,878). Relative cost-effectiveness was unchanged in 2005: $69,731 versus $79,576. The cost-effectiveness of both treatments improved in relation to projections by inflation. Sensitivity analyses suggest that the relative cost-effectiveness of TESE versus varicocelectomy can only be changed with either substantial improvement in spontaneous live delivery rates after varicocelectomy or with deterioration in IVF success rates. Microsurgical TESE appears to be more cost effective than varicocelectomy for treatment of varicocele-associated nonobstructive azoospermia when indirect costs are considered. The cost-effectiveness of both treatments has improved with time. These results may be tailored with institution-specific data to allow more individualized results.

Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome

To determine whether morbid obesity is associated with decreased pregnancy and live birth rates after IVF in women with polycystic ovary syndrome (PCOS). Retrospective cohort study. University-based fertility center. Seventy-two women with PCOS who completed their first IVF cycle between 2001 and 2006. Outcomes of IVF were compared between women with a body mass index (BMI) of <40 kg/m(2) vs. those with a BMI of > or =40 kg/m(2). Clinical pregnancy rate, live birth rate. Morbidly obese women with PCOS (n = 19) had significantly lower clinical pregnancy rates after IVF than patients with PCOS who were not morbidly obese (n = 53) (32% vs. 72%, relative risk 0.44, 95% confidence interval 0.22-0.87). Their live birth rates were lower too, although this difference was not statistically significant (32% vs. 60%, relative risk 0.52, 95% confidence interval 0.26-1.05). Morbid obesity is associated with lower pregnancy rates in women with PCOS after IVF, raising the question of whether weight loss may improve IVF success rates for morbidly obese PCOS patients.

Elasticity Measurement of Zona Pellucida Using a Micro Tactile Sensor to Evaluate Embryo Quality

To enable improved success rates of IVF, we developed the technology to optimize embryo selection with the highest implantation potential while ensuring no damage to embryos using zona elasticity as the selection criterion. In this communication we outline the biomechanics and safety of zona pellucida (ZP) elasticity measurement using the micro tactile sensor (MTS) system and demonstrate the specific changes in ZP elasticity during oocyte maturation, fertilization, and early embryo development. Zona hardening was demonstrated mechanically following fertilization at the pronuclear (PN) stage, and Young's modulus decreased gradually as the embryo developed. Evaluation of the quality of expanded blastocysts (EPB) showed that the quality of EPBs could also be evaluated from elasticity parameters. Furthermore, the observations indicated that ZPs of embryos generated in vivo were significantly harder than those of embryos generated in vitro at each stage. Preliminary results also indicated that denuded oocytes matured in vitro did not show zona hardening following parthenogenetic activation by strontium chloride, suggesting that sufficient maturation and consequent oocyte activation may be evaluated by increases in ZP elasticity. We conclude that MTS-elective single embryo transfer can be applied to human assisted reproductive technology to enable embryo quality evaluation in both early embryos and EPBs.

The Effect of Media Type, Gas Environment, and Incubator Model on IVF Success Rates

Objective: To optimize ongoing clinical pregnancy rates in an unselected IVF population, we retrospectively compared two different media formulations (P1/G1/G2 sequential and LifeGlobal medium), contrasted a 6% CO2 in air with a 6% CO2/5% O2/89% N2 gas incubator environment, and finally evaluated the effectiveness of two different types of incubators (Sanyo MCO-5M vs. Hearus 240). Over a 1-year period between April 2006 and March 2007, treatments were applied in quarterly increments. Methods: All patients experienced controlled ovarian hyperstimulation, followed by egg retrieval 35 h after hCG. Eggs were recovered and placed in P1 medium + 5% HSA until insemination. Eggs were moved to a more complex medium containing 5% HSA/5% SS after ICSI or after IVF fertilization check. Embryos were evaluated on day 3 and transfered on day 3 to 5 depending on the number/quality of embryos available and the IVF history of the patient. Transfers were performed under ultrasound guidance, primarily using a Wallace catheter. Results: Tabled 1Age <35 yr + donor cyclesAge <38 yr + donorsCategorynn (%) + b-hCGn (%) OngPregnn (%) + b-hCGn (%) OngPreg6% CO2/air incubation[2ndQrt06]P1/G1/G2 media4940 (82)aSignificant difference (P<.05) within column subsection.31 (63)aSignificant difference (P<.05) within column subsection.7554 (72)42 (56)[4thQrt06]Global medium4929 (59)24 (49)6542 (65)33 (51)6% CO2/5% O2/90% N2 incubation[1stQrt07]Sanyo Mini2922 (76)21 (72)aSignificant difference (P<.05) within column subsection.3825 (66)24 (63)[LG media]Heraeus 2402115 (71)13 (62)3224 (75)aSignificant difference (P<.05) within column subsection.20 (63)Combined TG5037 (74)34 (68)7049 (70)44 (63a Significant difference (P<.05) within column subsection. Open table in a new tab Conclusions: Overall, both the P1/G1/G2 sequential system and the LG all-in-one medium produced good pregnancy rates under standard 6% CO2 in air conditions. In contrast, the LG system with tri-gas incubation significantly improved pregnancy outcomes by reducing SABs and biochemical pregnancies (50% decrease), resulting in higher ongoing clinical pregnancy rates. No difference was observed in the type of incubator used; however, this is one of the first reports validating the clinical effectiveness of the new Sanyo mini-incubators.

Autoimmune response to Chlamydia trachomatis infection and in vitro fertilization outcome

This observational study was conducted in 235 patients undergoing IVF who had a cervical swab positive for Chlamydia trachomatis and who underwent antibiotic treatment until a negative cervical swab before IVF attempt. After oocyte retrieval, follicular fluids of 109 patients out of 228 still showed the presence of IgA antichlamydia antibodies and a significantly lower pregnancy and implantation rate; therefore we conclude that patients should undergo IVF procedure after serum antichlamydia IgA tests negative.

Tratamiento de acupuntura de preparación para una fertilización in vitro en un caso de infertilidad. Un estudio observacional

Background During the past years acupuncture has been increasingly used to assist in vitro fertilization (ivF). Objective To test whether success rates of acupuncture for ivF could be raised employing a semi-standardised acupuncture regimen with special emphasis on acupuncture point Ex-R8. Method During III/99 and III/06 261 female patients were treated with acupunctur directly before and after embryo transfer. Result 93 of 261 patients became pregnant (rise of β-HCG in the second week after transfer in 35,6 %). Discussion The success rate is especially impressive because the patients treated in my clinic had undergone at least one non successful ivF before. Conclusion There is no doubt that acupuncture is able to raise the success rate of ivF. I advise the scientific community to test my therapeutic regimen, especially including the utilisation of acupuncture point Ex-R 8.

Low negative affect prior to treatment is associated with a decreased chance of live birth from a first IVF cycle

Psychological variables, such as anxiety and depression, may have a negative impact on IVF outcomes, but the evidence remains inconclusive. Previous studies have usually measured a single psychological parameter with clinical pregnancy as the outcome. The objective of the current study was to determine whether pretreatment or procedural psychological variables in women undergoing a first IVF cycle affect the chance of achieving a live birth from that cycle. Between February 2002 and February 2004, 391 women with an indication for IVF were recruited at two University Medical Centres in The Netherlands. Pretreatment anxiety and depression were measured with the Hospital Anxiety and Depression Scale. The Daily Record Keeping Chart was used to measure negative and positive affect before treatment and daily during ovarian stimulation. Multiple stepwise forward logistic regression analysis was performed with term live birth as the dependent variable. Regression analysis showed that women who expressed less negative affect at baseline were less likely to achieve live birth (P = 0.03). After one IVF cycle, women who received a standard IVF strategy were more likely to reach live birth delivery than those who received a mild IVF strategy (P = 0.002). A male/female indication for IVF was associated with a higher chance of achieving term live birth than a female only indication (P = 0.03). Age, duration of infertility or type of infertility were not independent predictors of live birth. The relationship between psychological parameters and IVF success rates is more complex than commonly believed. The expression of negative emotions before starting IVF might not be always detrimental for outcomes.

Polypoid appearance of the endometrium on office hysteroscopy a significant predictor of miscarriage after IVF-ET

Endometrial lesions such as polyps, submucous myomas or adhesions may negatively affect the implantation and clinical pregnancy rates and may increase the abortion rates after IVF cycles. Polypoid appearance of the endometrium during luteal phase in absence of a typical solitary polyp is not uncommon. However, the relationship between polypoid appearance of the endometrium during luteal phase and IVF success rate and abortion rates have not been investigated previously. Our aim was to assess the impact of polypolid appearance detected by office hysteroscopy on clinical pregnancy and abortion rates in IVF cycles.

The percentage of abnormal embryos by PGD-AS negatively correlates with IVF success rate in young patients

Preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) has been offered to patients for more than a decade. The efficacy of PGD-AS is still controversial. Because PGD-AS is limited to evaluation of a single cell with limited numbers of chromosomes screened, normal results do not exclude abnormalities in other chromosomes in an embryo. Our hypothesis is that higher percentage of abnormal embryos by PGD-AS may reflect unidentified abnormalities in so-called “normal” embryos. Therefore, this study was to determine if a higher percentage of abnormal embryos by PGD-AS negatively correlates with clinical pregnancy rate.

Womb-on-a-chip could improve IVF success rate

Fertilisation inside a microfluidic “womb mimic” creates embryos that are more likely to survive

Cumulative live birth rates following IVF in 41- to 43-year-old women presenting with favourable ovarian reserve characteristics

For women aged 41–43 years old, success rates in IVF are generally poor. This study aimed to assess cumulative live birth rate related to treatment costs over a maximum of three IVF cycles in selected women who were considered to still have adequate ovarian reserve. Fifty-five patients (38% of the total cohort, n = 144) were excluded from IVF treatment based on low antral follicle count (<5 follicles) and/or elevated basal FSH (>15 IU/l). Of those admitted, 66 (74%) actually started and completed a total of 125 IVF/intracytoplasmic sperm injection cycles. Treatment resulted in 10 live births (8% per cycle). Kaplan-Meier survival analysis revealed a realistic cumulative live birth rate after three cycles of 17%. The direct medical costs per live birth were calculated to be approximately €44,000. These results show that selection towards favourable ovarian reserve status in the female age group 41–43 years yielded disappointing results in terms of cumulative live birth rates after IVF. In view of the costs raised per live birth, improvement of selection parameters for treatment in this age group is warranted.

Akupunkturbehandlung zur Vorbereitung auf eine In-vitro-Fertilisation bei unerfülltem Kinderwunsch – eine Anwendungsbeobachtung

BackgroundDuring the past years acupuncture has been increasingly used to assist in vitro fertilization (ivF). ObjectiveTo test whether success rates of acupuncture for ivF could be raised employing a semi-standardised acupuncture regimen with special emphasis on acupuncture point Ex-R8. MethodDuring III/99 and III/06 261 female patients were treated with acupunctur directly before and after embryo transfer. Result93 of 261 patients became pregnant (rise of b-HCG in the second week after transfer in 35,6 %). DiscussionThe success rate is especially impressive because the patients treated in my clinic had undergone at least one non successful ivF before. ConclusionThere is no doubt that acupuncture is able to raise the success rate of ivF. I advise the scientific community to test my therapeutic regimen, especially including the utilisation of acupuncture point Ex-R 8.

Emerging technologies for the molecular study of infertility, and potential clinical applications

The techniques currently used to treat infertility cases are quite limited in their capabilities, due to an incomplete understanding of the molecular activities of germ cells. Fortunately, several technologies are presently being researched that should aid in the understanding of the various molecular causes of germ cell pathologies. This review discusses microarray technology, proteomics, metabolic profiling, the PolScope, atomic force microscopy and microfluidics. These technologies have all seen success in preliminary studies, and promise directly or indirectly to improve the low success rates of IVF and other related therapies. However, their widespread use in laboratories and clinics may not be seen until preliminary studies confirming their safety and effectiveness are published, and until standardized protocols for their utilization are established.

The problem of multiple pregnancies

A meeting of experts on the subject of multiple pregnancies was held on 25 November 2005 at the invitation of the Bertarelli Foundation, Switzerland. Swiss law on reproductive medicine prohibits the selection of embryos, a situation that not only reduces the success rate of IVF, but also makes it virtually impossible to achieve a further reduction in multiple pregnancy rates resulting from IVF. The medical profession, the couples affected and the general public need to be better informed about this restrictive law. Furthermore, it is a little known fact that a considerable number of multiple pregnancies are due to simple ovulation induction.

O-10: Prospective randomized trial of autologous endometrial coculture versus traditional IVF: An interim analysis

One factor that may contribute to the poor success rates in IVF may be the suboptimal culture conditions in which fertilization and early embryonic growth occur. A significant amount of research has focused on tailoring the in vitro culture media to the requirements of the human embryo. Unfortunely, these media are devoid of many factors expressed in vivo (ie growth factors). Therefore, in an effort to more closely mimic the in vivo preimplantation environment the growth of embryos on a layer of cells has been developed (coculture).