IVF Program Research Articles

Estrogen metabolites in human corpus luteum physiology: differential effects on angiogenic activity

To determine tissue concentrations of E2, estrone, P, and estrogens metabolites (EMs) 2-methoxyestradiol, 2-methoxyestrone, 4-hydroxyestrone, and 16-ketoestradiol in corpus luteum (CL) of different ages, and after hCG administration; and to examine the effects of EMs on vascular endothelial growth factor (VEGF) secretion and angiogenic activity released by cultured luteinizing granulosa cells in the presence and absence of hCG. Experimental study. University. Thirty-two healthy women of reproductive age. Corpus luteum was collected at the time of minilaparotomy for tubal sterilization, at varying stages of the luteal phase (LP). Late-LP CL was collected 24hours after IM administration of 10,000 IU hCG. Granulosa cells were isolated from follicular aspirates obtained from healthy women participating in our IVF program for male factor infertility. Estrogen metabolite concentrations were determined in CL tissue, and VEGF was assessed in conditioned medium. The angiogenic activity was analyzed by bioassay. Concentrations of EMs with proangiogenic activity (16-ketoestradiol and 4-hydroxyestrone) were higher in early and mid-LP CL vs. late-LP CL. These EMs and hCG increased VEGF production and angiogenic activity. Conversely, late-LP CL had significantly higher levels of 2-methoxyestrone and 2-methoxyestradiol, which have antiangiogenic activity. Administration of hCG reduced the production of these EMs. Our findings suggest that the EMs are important paracrine modulators of CL function. Administration of hCG increases the production of EMs with proangiogenic activity and reduces the secretion of those EMs with antiangiogenic action, suggesting a novel mechanism by which the late-LP CL is rescued in conception cycles.

Women show a higher level of anxiety during IVF treatment than men and hold different concerns: a cohort study.

The aim of the present study was to determine levels of anxiety during the course of IVF treatment and gender differences in treatment anxiety. This was a prospective cohort study set in a university affiliated, tertiary care IVF program. 119 women and 82 men entering the clinic to undergo IVF treatment filled out questionnaires containing the Spielberger state-trait-anxiety-inventory (STAI) as well as further items on specific stress triggers. Women and men undergoing IVF have higher levels of anxiety than the average population in Germany. Overall, female patients show significantly higher values (mean ± SD) for state and trait anxiety (47.4 ± 11.0 and 40.1 ± 9.85) than their male partners (41.4 ± 9.66 and 35.3 ± 8.57, p < 0.01). Over the course of several IVF cycles, average STAI scores increased for both genders. When asked about specific stress factors on a 4-point scale from 'not at all' to 'very much so', women report as their main anxiety the failure to achieve a successful pregnancy, scoring significantly higher on questions like 'obtaining a negative pregnancy test' (3.24 ± 0.82, p < 0.01) and 'disclosure of infertility' (3.02 ± 1.10, p < 0.001). Their male partners are more concerned about the health risks the women have to take such as 'side effects of ovarian stimulation' (2.55 ± 0.77, p = 0.002) and 'bleeding or infection after the oocyte aspiration' (2.58 ± 0.84, p = 0.007). Both genders indicated to be very little worried about multiple pregnancies after IVF. Women show a higher level of anxiety during IVF treatment and hold different concerns. Neither of the sexes appears to be familiar with the risks associated with multiple pregnancies, a matter that should better be addressed.

Intravenous intralipid therapy is not beneficial in having a live delivery in women aged 40-42 years with a previous history of miscarriage or failure to conceive despite embryo transfer undergoing in vitro fertilization-embryo transfer

Purpose: To evaluate the efficacy of intralipid intravenous infusion in achieving a live pregnancy following IVF – embryo transfer in women of advanced reproductive age (40-42 years). Materials and Methods: A matched control was performed. Women aged 40-42 with a previous history of miscarriage or who failed to conceive despite previous embryo transfer who entered an IVF program were offered intravenous intralipid therapy (four ml of 20% liposyn II in 100 ml normal saline over one hour) during the mid-follicular phase. Clinical pregnancy rates (eight weeks with viable gestation) and live delivered pregnancy rates were then determined and compared. Results: The results were evaluated after ten matched cycles. There were no clinical pregnancies in those receiving intralipid vs. a 40% clinical and a 30% live delivered pregnancy rate in the untreated controls (p = 0.087, Fisher’s exact test). The study was terminated because of these preliminary data. Conclusions: In the test tube, adding intralipid to natural killer cells can inhibit their cytolytic action. However, the use of intravenous intralipid to suppress natural killer cell activity does not seem to improve the chance of a live delivery in women aged 40-42 years with a previous history of miscarriage. In fact this therapy may actually be detrimental in this age group. Since efficacy of this therapy was not found in a group of advanced reproductive age, it is not clear why this should be effective for a younger population. A controlled study for the younger group is needed. Perhaps such a study could be limited to only those with miscarriage rather than also concluding failure to conceive despite embryo transfer. Intralipid failed to improve live delivered pregnancy rates in women with prior miscarriage or previous failure with embryo transfer.

Психологические характеристики женщин, проходящих лечение по программе ЭКО

Open Access In Russian (Abstract and References in English) The objective. To find specificities of mental states, personal and reactive anxiety, dominating reproductive motives in women, who participate in an IVF programme taking into account the time of planned pregnancy, number of IVF attempts and success of treatment. Patients and methods. The study included 214 women who participated in an IVF programme and 83 women with natural pregnancy. The following psychodiagnostic techniques were used: «Self-evaluation of mental states» (according to H.Eysenck), «Depression inventory» (A.Beck), anxiety scale (Ch.Spielberger, adapted by Yu.L.Khanin), reproductive motives questionnaire «My pregnancy» (O.V.Magdenko). Results. Mental states of most women of the IVF group are characterized by allowable levels of anxiety, rigidity, aggression and frustration. In 30% of women, symptoms of mild, moderate, medium, in single cases – severe depression are noted. High personal anxiety is characteristic of many women of the IVF group. No relationship between mental states and the number of IVF attempts and outcomes of treatment has been found. We have found that a longer planning of pregnancy is associated in women of the IVF group with increased frustration and significance of certain motives. The latent structure of the examined psychological characteristics in women of the IVF group is presented by four factors pointing to possible psychological predictors of the formation of negative mental states. Conclusion. The results we have obtained about the psychological characteristics of women objectify the tasks of a differentiated psychological follow-up of women during an IVF programme indicating the need for replication on other samples and further research with due account of the heterogeneity of an IVF group. Key words: heterogeneity of women of IVF group, women participating in IVF programme; personal and reactive anxiety, mental states, reproductive motives.

A priority of gonadotropin selection for ovarian stimulation in IVF programs

A priority of gonadotropin selection for ovarian stimulation in IVF programs

IVF program in HIV-infected patients (patient selection and characteristics)

IVF program in HIV-infected patients (patient selection and characteristics)

OOCYTE FINAL MATURATION TRIGGERS IN IVF PROGRAMS

A trigger is a firing key (Lat. trigger). A luteinizing hormone is this trigger – a trigger of ovulation at a certain cycle of the ovarial cycle. Understanding of the trigger problem in the artificially cycles of IVF programs requires recollection of certain theoretical issues of follicle growth and maturation as well as the ovulation process in the natural ovarian cycle [1, 2].

Follicular fluid Vascular Endothelial Growth Factor (VEGF) could be a predictor for pregnancy outcome in normo-responders and polycystic ovary syndrome women undergoing IVF/ICSI treatment cycles

Abstract Objective: The aim of this study was to evaluate the serum and follicular fluid levels of Vascular Endothelial Growth Factor (VEGF) as possible predictive markers for IVF outcome in PCOS patients. Design: Prospective cross-sectional study. Materials and Methods: Forty patients with PCOS and 40 age and weight matched control women were included in this study. All of them were enrolled in the IVF program. Blood and follicular fluid (FF) samples were collected from all subjects on the day of oocyte retrieval. VEGF levels were measured in serum and follicular fluid (FF) using enzyme linked immunosorbent assay (ELISA). The correlation between VEGF levels and number of retrieved oocyte, number of mature oocyte, number of fertilized oocyte, number of embryos, percent of mature oocytes, fertilization rate and pregnancy was assessed. Results: PCOS patients showed higher serum VEGF levels than controls (297.46 ± 159.45 pg/ml vs. 134.08 ± 113.06 pg/ml, p value = 0.0001) and higher FF VEGF levels compared to controls (1358.92 ± 820.86 pg/ml vs. 987.58 ± 236.62 pg/ml, p value = 0.007). Serum VEGF levels were not significantly correlated with the number of retrieved oocyte in both PCOS ( r = 0.37, p value = 0.19) and control women ( r = −0.03, p value = 0.83), and FF VEGF levels were not significantly correlated with the number of retrieved oocyte in both PCOS ( r = −0.06, p value = 0.7) and control women ( r = −0.13, p value = 0.43). Both serum and FF VEGF levels were not significantly correlated with the number of mature oocyte, number of fertilized oocyte, number of embryos, percent of mature oocytes or fertilization rate. Serum VEGF levels were not significantly different between pregnant and non-pregnant women in both PCOS (256.69 ± 139.11 pg/ml vs. 300.20 ± 114.60 pg/ml, p value = 0.416) and control women (107.98 ± 115.51 pg/ml vs. 154.39 ± 111.09 pg/ml, p value = 0.271), whereas FF VEGF levels were significantly lower in FFs from the group of pregnancy than those from the group of no-pregnancy in both PCOS (812.04 ± 308.16 pg/ml vs. 1936.78 ± 771.79 pg/ml, p value = 0.0001) and control women (822.45 ± 199.45 pg/ml vs. 1171.98 ± 139.60 pg/ml, p value = 0.0001). FF VEGF levels had a significant predictive value of pregnancy in both PCOS ( p value = 0.0001) and control women ( p value = 0.0001). Conclusion: FF VEGF levels may serve as a reliable predictive marker for pregnancy in both normal women and women with polycystic ovary syndrome undergoing IVF.

249 OPTIMIZING DONOR EFFICIENCY WITH FOLLICLE STIMULATING HORMONE SUPERSTIMULATION IN A COMMERCIAL IN VITRO FERTILIZATION PROGRAM IN HOLSTEINS

Commercial IVF programs in Holstein (HO) donors in North America require that not only quantity, but also quality of embryos be increased. These programs are intended to produce the maximal number of offspring from elite females and males over a short period of time. Optimal embryo quality is needed for cryopreservation (for embryo trade and a recurrent problem with a shortage of recipients) and to maximize the number of pregnancies. Preliminary studies in our laboratory showed a significant increase in blastocyst rates following superstimulation with FSH (42 v. 22%; P &lt; 0.0001). The objective of this presentation is to describe parameters of practical importance that affect donor efficiency in an IVF program that involves superstimulation. Data from commercial IVF records were retrospectively analysed. All in-house HO donors admitted since 2013 and at least 12 months of age at the time of collection were included. In total, 1387 ultrasound-guided follicle aspirations (ovum pickup) were performed on 376 HO donors following a constant dose, 6 injections, pFSH (Folltropin-V, Vetoquinol) protocol with a 30- to 43-h coasting period. The IVF system included maturation of cumulus-oocyte complex in TCM-199 based medium, fertilization with frozen‐thawed unsexed, sexed, and reverse-sorted semen, as well as culture in modified synthetic oviduct fluid under mineral oil in a humidified atmosphere containing 6.9% CO2, 5% O2, and 88.1% N2 at 38.5°C for 7 days. Antral follicular counts (AFC), assessed with a 7.5-MHz endovaginal ultrasound probe at random stages during diestrus, were correlated with the number of follicles stimulated. Average number of follicles stimulated was 13.9 (median = 12, maximum = 111) with 74.6% of follicles between 7 and 15 mm at the time of ovum pickup. Average recovery rate was 73.2% and tended to decrease as size of the follicles increased. Transferable embryos rate (TER), defined as the number of IETS quality 1 and 2 embryos produced out of the number of oocytes placed in maturation per ovum pickup session, was 42.1% (median = 43.7%, maximum = 100%). Nearly two-thirds of the transferable embryos produced met our freezability criteria. When these frozen embryos were transferred, over 60% of the recipients were pregnant at 30 days. No difference was observed in efficiency of pregnant versus open donors for TER. In most donors, OPU were repeated every 2 weeks, regardless of pregnancy status. The effect of multiple stimulations on the ability of a donor to maintain its efficiency was assessed by comparing number of follicles stimulated and TER in the first and last 3 collections in donors that had at least 10 collections, with no significant difference. Individual variation appeared very high, as approximately one-third of the donors produced two-thirds of the embryos. When defining a poor responder based on the number of follicles available for ovum pickup following superstimulation, TER was lower in donors with &lt;6 follicles and &gt;18 follicles. Data suggest that HO donors with high AFC are more efficient in an IVF program following superstimulation because of a possible greater oocyte competence.

The value of different ovarian reserve tests in the prediction of ovarian response in patients with unexplained infertility

Abstract Background: Ovarian reserve tests in unexplained infertility patients before management either by ovulation induction or IVF program are a worthy procedure as it saves unnecessary procedures, induction complications, canceled cycles, wasted resources and emotional stress to the couple in case of low estimate, and can as well help in adjusting the doses to obtain the most appropriate response. Aim of work: To determine the value of mean ovarian volume, AFC, maternal age, FSH and AMH in infertile patients undergoing ovulation induction or IVF cycles. Primary outcome is to predict the best parameter of ovarian reserve. Design: Prospective cross-sectional study. Patients and methods: One hundred infertile women received treatment in the form of induction of ovulation and timed intercourse/IUI or IVF. They had basal FSH, AMH, AFC and mean ovarian volume assessment. The response was then evaluated according to the number of follicles on the day of hCG or the number of oocytes retrieved in IVF cycles. Results and conclusion: The total AFC and AMH are found to correlate significantly with the ovarian response with p values

Influence of obesity on sperm DNA fragmentation index and outcomes of IVF programs

The reduction of the birth rates in the developed countries and increase in the frequency of male infertility stimulate the extensive investigations for the factors that negatively affect the reproductive system of the men and causing their infertility. The excessive body weight and obesity in the men of the reproductive age can promote the development of infertility. One of the mechanisms by which excess fat tissue has a negative impact on male fertility is disturbance of spermatogenesis. The authors aggregate scientific publications concerning the macroscopic and ultrastructural disturbances of spermatogenesis in men with obesity. We present the results of the study conducted at the Department of ART Endocrinology Research Center, targeted at the revelation of the relationship of body mass index of men of reproductive age, semen parameters, sperm DNA fragmentation index, as well as the influence of body mass index on outcomes of in vitro fertilization programs.

The role of genetic and autoimmune factors in poor ovarian response in IVF programs

Background: The poor ovarian response (POR) to ovarian stimulation significantly decreases the efficiency of assisted reproduction technologies. The genesis of POR is not well understood, and can result from various genetic and immune factors.Purpose: To determine the role of genetic (number of CGG repeats in the FMR1-gene) and autoimmune factors (anti-ovarian antibodies) in POR in IVF programs.Methods: In a cross-sectional study, 150 infertile women were divided into the POR group (n = 65) and the group with a normal ovarian response (n = 85). All the patients underwent the detection of CGG repeats in the FMR1-gene by polymerase chain reaction, serum anti-zona pellucida antibodies (AZPA) and anti-ovarian antibodies by enzyme-linked immunosorbent assay.Results: The risk of POR was higher in patients with CGG counts > 34, but not in the patients with CGG counts < 26. The higher level of AZPA was found in the patients with the 26–34 CGG repeats compared to the patients with <26/> 34 CGG repeats.Conclusion: A higher number of CGG repeats in the FMR1-gene may be a risk factor of POR in IVF programs. Normal CGG counts in regard to ovarian reserve (26–34) suggest the autoimmune-driven POR.

EFFICACY OF SURGICAL SPERM RETRIEVAL IN AZOOSPERMIC PATIENT AND ITS CONTRIBUTION TO IN VITRO RERTILIZATION PROGRAM

Objective: This study was made to evaluate efficacy and success rate of Percutaneous Epididymal Sperm Aspiration (PESA), Microsurgical Epididymal Sperm Aspiration (MESA), or Testicular Sperm Extraction (TESE) in azoopsermic patients, and evaluate IVF program’s pregnancy rate by comparing methods of sperm retrieval. Material &amp; method: A descriptive retrospective study to azoospermic patients undergone PESA, MESA or TESE and IVF program in Bunda Hospital Jakarta and Cipto Mangunkusumo Hospital Jakarta in 2011–2012. The data were collected from patients’ medical records and IVF program’s database. Results: There were 146 azoospermic patients with mean age 38.97 ± 7.35 years. Viable sperm was found in 46 patients (31.5%) by PESA and 47 patients (32.2%) by MESA and TESE. The IVF program was followed by 72 patients. Sperm was retrieved by PESA in 43 patients (59.7%) and TESE in 29 patients (40.3%). Pregnancy was achieved in 18 patients in PESA group (25%) and 15 patients (20.8%) in TESE group. Conclusion: Sperm can be retrieved from azoospermic patients by PESA, MESA or TESE, and there was good success rate in pregnancy rate of IVF program by using surgically retrieved sperm.

Using 24-chromosome aneuploidy test and frozen blastocyst transfer cycles significantly improves pregnancy rate and decreases miscarriage rate in IVF programs

The purpose of this study was to compare clinical outcomes (pregnancy and miscarriage rates) between frozen blastocyst transfer (FBT) cycles without preimplantation genetic screening (PGS), FBT cycles with 24-chromosome aneuploidy test and FBT cycles with 9-chromosome screening for infertile patients with normal karyotype aged 25-45.

Improvement in pregnancy rates in immunologically infertile men undergoing prednisolone and IVF programs preceded by sperm penetration assay

viewed. Only the first SA was evaluated per patient. RESULTS: In total, 901 SA including 276 who worked in Business/ Finance/Sales (30.6%), 224 worked in Information Technology (24.9%), 77 were engineers (8.5%), 51 worked in government (5.7%), and 37 in Health Care (4.1%). There were no differences in any semen parameter among different occupations; specifically IT use was not associated with any negative effects on seminal parameters. CONCLUSIONS: Men working in IT have no differences in seminal parameters compared to other white collar occupations. There were no differences among the different occupations evaluated, a reassuring novel finding. As far as we know, this is the largest study evaluating the effects of various occupations, including those that require significant sitting such as IT, on semen parameters.

Association of prepubertal serum dioxin concentrations with semen quality in a prospective cohort of young Russian men

aspect of infertility care. RESULTS: Our findings were that classical economic drivers relating to wealth or economic well-being were not predictive of IVF demand. Rather, IVF demand was best predicted by general medical insurance coverage, specific IVF coverage, and the proportion of the population with a selfidentified Catholic background in a state. The model constructed was: Log(IVF Cases/Pop.) 1⁄4 -2.96 + 2.41 Catholic + 2.88 Insurance Coverage + 0.43 IVF Coverage (se) (1.05) (0.72) (1.33) (0.17) (p-value) (0.007) (0.0018) (.036) (0.015) The F-statistic was 16.2; and the R-squared was 0.53. CONCLUSIONS: Independent variables associated with various measures of income and economic outlook were not helpful in explaining the variability of IVF utilization among states. The number of IVF cases done in a state was not related to the effectiveness of IVF in that state nor the convenience of having an increased number of IVF programs. The most unexpected finding was that a 1% increase in the proportion of self-identified Catholics in a state was associated with a 2.4% increase in the number of IVF cases per 1000 reproductive aged women. Given the Donum Vitae, one might have expected the impact of an increased proportion of Catholics to have a negative impact on IVF utilization. We hypothesized that the variable of being a self-identified Catholic encompassed microeconomic factors that played a major role in the decision to undertake IVF. These might include love of family and an increased desire to have children.

The effect of a publicly fundeded North American IVF program with mandated single embryo transfer on maternal antenatal admission rates

The effect of a publicly fundeded North American IVF program with mandated single embryo transfer on maternal antenatal admission rates

Influence of seminal quality in donor egg IVF program using vitrified oocytes

Influence of seminal quality in donor egg IVF program using vitrified oocytes

Live births achieved via IVF are increased by improvements in air quality and laboratory environment

Infertility is a common disease, which causes many couples to seek treatment with assisted reproduction techniques. Many factors contribute to successful assisted reproduction technique outcomes. One important factor is laboratory environment and air quality. Our facility had the unique opportunity to compare consecutively used, but separate assisted reproduction technique laboratories, as a result of a required move. Environmental conditions were improved by strategic engineering designs. All other aspects of the IVF laboratory, including equipment, physicians, embryologists, nursing staff and protocols, were kept constant between facilities. Air quality testing showed improved air quality at the new IVF site. Embryo implantation (32.4% versus 24.3%; P < 0.01) and live birth (39.3% versus 31.8%, P < 0.05) were significantly increased in the new facility compared with the old facility. More patients met clinical criteria and underwent mandatory single embryo transfer on day 5 leading to both a reduction in multiple gestation pregnancies and increased numbers of vitrified embryos per patient with supernumerary embryos available. Improvements in IVF laboratory conditions and air quality had profound positive effects on laboratory measures and patient outcomes. This study further strengthens the importance of the laboratory environment and air quality in the success of an IVF programme.

Risks of conservative management in women with ovarian endometriomas undergoing IVF.

Classical surgical management of endometriotic ovarian cysts using the laparoscopic stripping technique has been recently questioned because of the surgical-related injury to the ovarian reserve. Accordingly, available guidelines suggest that endometriomas with a mean diameter below 4 cm should not be systematically removed before IVF procedures. However, conservative management may have some potential drawbacks and risks. The presence of the endometrioma may theoretically interfere with ovarian responsiveness to hyperstimulation and oocyte competence, the retrieval of the oocytes may be more difficult and risky, the disease may progress during the procedure, pregnancy outcome may be affected and there is the risk of missing occult malignancies with cancer development later in life. In the present review, we aimed at assessing whether these risks do exist and, if so, at estimating their clinical relevance. We searched PubMed for articles published in the English language between January 1990 and August 2014 that reported on endometriomas and assisted reproductive techniques. Special care was given to studies reporting data purporting to distinguish the effects of ovarian endometriomas per sé from those consequent to surgery for endometriosis or from endometriosis in general. Based on the evidence reviewed in the present study, it can be concluded that conservative management may actually expose women to four of the following theoretical risks, i.e. infection of the endometriomas, follicular fluid contamination with the endometrioma content, higher risk of pregnancy complications and cancer development later in life. The first three conditions do not justify surgery because these events are uncommon and the number of women needed to be treated would be exceedingly high and would not justify the costs and risks of the intervention. Albeit also very rare, the possibility of developing ovarian cancer later in life is more troublesome because it is a life-threatening condition. However, this alarmism is supported by only one cohort study and this risk can be effectively prevented by postponing surgery until after the IVF programme is concluded or when women have definitely satisfied their reproductive wishes. The available evidence on the risks of conservative management does not support systematic surgery before IVF in women with small ovarian endometriomas.