Ákos Murber

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

BackgroundDespite 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.MethodsBetween 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 Wilcoxons matched pairs rank sum test and McNemars chi-square test. P < 0.05 was considered statistically significant.ResultsThe 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).ConclusionAntagonist 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.

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.

Importance of cytoplasmic granularity of human oocytes in In vitro fertilization treatments

The aim of this study was to examine the effect of different stimulation protocols on oocyte granularity and to determine the influence of cytoplasmic granularity on further embryo development. A total of 2448 oocytes from 393 intracytoplasmic sperm injection (ICSI) cycles were analysed retrospectively. Oocytes were classified into 5 groups according to cytoplasmic granularity. (A) no granule or 1-2 small (<5 μm) granules; (B) more than 3 small granules; (C) large granules (>5 μm); (D) refractile body; (E) dense centrally located granular area. Correlation between characteristics of hormonal stimulation, oocyte granularity and embryo development was analysed. The occurrence of cytoplasmic granularity was influenced by the patients age and characteristics of stimulation. The type of granulation had no effect on fertilization rate and zygote morphology. However, some type of granulation resulted in a lower cleavage rate and more fragmented embryos. Our results provided additional information on how hormonal stimulation affects oocyte quality. While cytoplasmic granularity seems not to have an effect on fertilization and embryo development, the presence of refractile body in the oocyte is associated with reduced cleavage rates and impaired embryo development.

Impact of highly purified versus recombinant follicle stimulating hormone on oocyte quality and embryo development in intracytoplasmic sperm injection cycles

The quality of oocytes and developing embryos are the most relevant factors determining the success of an in vitro fertilization (IVF) treatment. However, there are very few studies analyzing the effects of different gonadotrophin preparations on oocyte and embryo quality. A retrospective secondary analysis of data collected from a prospective randomized study was performed to compare highly purified versus recombinant follicle stimulating hormone (HP-FSH vs. rFSH). The main outcome measures were quantity and quality of oocytes and embryos, dynamics of embryo development, cryopreservation, clinical pregnancy and live birth rate. The number of retrieved and of mature (MII) oocytes showed no significant differences. Fertilization rate was significantly higher in the HP-FSH group (68.9% vs. 59.9%, p = 0.01). We also found significantly higher rate of cryopreserved embryos per all retrieved oocytes (23.4% vs. 14.5%, p = 0.002) in the HP-FSH group. There were no significant differences in clinical pregnancy and in live birth rates. Oocytes obtained with HP-FSH stimulation showed higher fertilisability, whereas pregnancy and live birth rates did not differ between the groups. However, patients treated with HP-FSH may benefit from the higher rate of embryos capable for cryopreservation, suggesting that cumulative pregnancy rates might be higher in this group.

Serum CA-125 and inhibin B levels in the prediction of ovarian response to gonadotropin stimulation in in vitro fertilization cycles.

There is much controversy about the relationship between serum CA-125 levels during in vitro fertilization (IVF) cycles and ovarian function. To evaluate the prognostic value of serum CA-125 and inhibin B measurements in predicting ovarian response to gonadotropin stimulation, we compared the CA-125 and inhibin B levels of poor and normal responders on the first day of ovarian stimulation, on the day of ovulation induction (OI) and at oocyte pick-up. Sixteen patients with poor ovarian response ( ⩽ 3 oocytes, serum estradiol (E2) ⩽ 900 pg/ml at OI) in IVF/intracytoplasmic sperm injection cycles were matched with normal responders ( ⩾ 6 oocytes, E2 ⩾ 1800 pg/ml) by age, spontaneous cycle day-3 follicle-stimulating hormone level and cause of infertility. Inhibin B concentrations were significantly lower at all three time points in poor responders, but CA-125 levels were not. No statistically significant correlation was found between CA-125 levels and any of the clinical or laboratory parameters examined. Thus, CA-125 measurements during stimulation are not useful in predicting or identifying poor ovarian response to gonadotropin stimulation in IVF cycles. The lack of difference in CA-125 concentrations between poor and normal responders and lack of correlation with E2 or inhibin B levels suggest that ovarian steroidogenesis and other granulosa cell functions do not influence the production of CA-125. Inhibin B, however, seems to predict ovarian response as early as at the start of stimulation.

Prognostic value of serum CA-125 measurements on stimulation day 1 and on the day of oocyte pickup in the prediction of IVF treatment outcome

Purpose: To assess whether serum levels of CA-125, a proposed marker of endometrial receptivity, are associated with pregnancy after IVF.Methods: 42 IVF pregnancies were matched with nonpregnant controls. Twenty-eight additional unmatched pregnancies were included for the comparison of pregnancy outcomes. CA-125 concentrations were measured on stimulation day 1 (SD1) and at oocyte pickup (OPU). We analyzed association between CA-125 levels and establishment of pregnancy and its outcome; correlation between CA-125 concentrations and other parameters; differences in CA-125 levels between SD1 and OPU.Results: In pregnant, but not in nonpregnant patients, CA-125 levels decreased significantly from SD1 to OPU. There was no significant difference in CA-125 levels at either time point between pregnant and nonpregnant subjects. No significant correlation was found between CA-125 levels and any other clinical or laboratory parameters.Conclusions: CA-125 measurements at the beginning of stimulation or at oocyte retrieval are not useful in predicting IVF outcome.

Az ovarialis hiperstimulációs szindróma kórélettana és korszerű 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.

Luteal-phase inhibin A and follicular-phase inhibin B levels are not characteristic of patients with an elevated LH-to-FSH ratio

AbstractPurpose: To test whether serum inhibin levels are related to differences in gonadotropin concentrations between patients with an elevated LH-to-FSH ratio (ELF patients) and controls. Methods: 32 ELF patients were matched with controls by age, body mass index (BMI), and cycle length. Results: No statistically significant difference was found in follicular-phase inhibin B levels or midluteal inhibin A levels between cases and controls. Significant negative correlation was observed between follicular-phase inhibin B concentrations and BMI in ELF patients but not among controls. LH and FSH were positively related to inhibin B levels in ELF patients. Midluteal inhibin A correlated with sex hormone-binding globulin in controls but not in ELF patients. Conclusions: Neither follicular-phase inhibin B levels nor midluteal inhibin A levels are characteristic of patients with an elevated LH-to-FSH ratio. Opposite correlations with LH and BMI suggest dysregulation of inhibin secretion rather than dimeric inhibins having a central role to the endocrinological imbalance observed in polycystic ovary syndrome.