Oocyte Maturation In Patients Research Articles

Spironolactone use and oocyte maturation in patients undergoing controlled ovarian hyperstimulation.

To evaluate the association between spironolactone use and controlled ovarian hyperstimulation (COH) outcomes. Retrospective study, including patients who underwent COH. Oocyte yield and maturation rates were compared by categories of spironolactone use at the start of their cycle. 402 patients were included. 83 patients continued spironolactone, 44 patients discontinued spironolactone, and 275 matched control patients were spironolactone-naïve. No difference was observed in the number of oocytes retrieved (17 ± 14 vs. 15 ± 13, p = 0.4) or mature oocytes vitrified (15 ± 9.5 vs. 12 ± 11, p = 0.4) in patients who continued spironolactone use and spironolactone naïve patients, respectively. When comparing patients who continued spironolactone use and patients who discontinued spironolactone use, no difference was seen in the number of oocytes retrieved (17 ± 14 vs. 17.5 ± 7.8, p = 0.9) or mature oocytes vitrified (15 ± 9.5 vs. 13.5 ± 6.5, p = 0.5), respectively. There was no observed relationship between total daily spironolactone dose (< 100mg/day, 100mg/day, 150mg/day and > 200 mg/day) and the total number of mature oocytes vitrified (respectively, 14.0 ± 13.0, 16.0 ± 7.8, 14.0 ± 4.5, 11.0 ± 7.0 oocytes, p = 0.4). This is the first study to evaluate the association between spironolactone and oocyte yield and maturation rates during COH cycles. These findings can assist in counseling patients on the implications of continuing spironolactone during COH cycle.

The possible regulatory role of miR-514 and miR-642b in cumulus cells on the oocyte maturation in patients with polycystic ovary syndrome

Polycystic ovary syndrome is a common endocrine disorder in reproductive-age women. Accordingly, abnormal microenvironment may negatively influence oocyte developmental competence as a result of the altered expression profile of cumulus cells (CCs), mainly the key players of oocyte maturation, such as epidermal growth factor receptor (EGFR) and prostaglandin E receptor-2 (PTGER2). This study aimed to examine the expression levels of miR-514, miR-642b, and their candidate target genes (EGFR and PTGER2, respectively) in CCs of immature and mature oocytes in patients with PCOS. A total of 40 oocytes at germinal vesicle (GV) and 40 oocytes at metaphase II (MII) stages were retrieved from 30 PCOS women. Quantitative real-time PCR was performed to analyze the expression level of miR-514, miR-642b, EGFR, and PTGER2 in cumulus cells (CCS) of each oocyte. The expression level of miRNAs and their candidate target genes were compared between CCs of GV and MII oocytes. Our study suggests an inverse relationship exists between the expression levels of miR-514 and EGFR, and miR-642b and PTGER2. Furthermore, we observed that CCs of GV oocytes had higher levels of EGFR and PTGER2 mRNA and lower levels of miR-514 and miR-642b expression compared to those of MII oocytes. The present study demonstrated that miR-514 and miR-642b can regulate oocyte development by targeting EGFR and PTGER2, respectively. Therefore, examination of these miRNAs in CCs could be promising parameters to predict oocyte competence in PCOS patients.

The Mechanism of Acentrosomal Spindle Assembly in Human Oocytes

ABSTRACT During somatic cell mitosis and meiosis, spindle assembly is an essential step for ensuring accurate chromosome transmission and is mediated via duplicated centrosomes. In nonsomatic cells, canonical centrosomes are absent in the oocytes of many species, suggesting the mechanism of female meiotic spindle assembly is not conserved between species. Human oocytes lack detectable acentriolar microtubule organizing centers at the meiotic spindle poles and the exact mechanism of acentrosomal spindle assembly in human oocyte remains unclear. This study aimed to utilize 3-dimensional (3D) high-resolution imaging of more than 2000 human oocytes to identify and characterize key structures in the spindle assembly process. First, human oocytes were stained to visualize chromosomes, kinetochores, and microtubules before maturation. Approximately 2 to 4 hours following nuclear envelope breakdown (NEBD), the nucleation of spindle microtubules was initiated from kinetochores. To identify factors driving this spindle microtubule nucleation from kinetochores in human oocytes, 86 human centrosome and microtubule-related proteins were localized by immunofluorescence in more than 1000 fixed human oocytes. Of these, 43 proteins localized in the meiotic spindle, among which 4 proteins (centriolar coiled-coil protein 110 [CCP110], cytoskeleton-associated protein 5 [CKAP5], disrupted in schizophrenia 1 [DISC1], and transforming acidic coiled-coil-containing protein 3 [TACC3]) showed kinetochore and spindle microtubule localization. It was observed that these 4 proteins belong to the same structure (human oocyte microtubule organizing center [huoMTOC]), and a dense microtubule cluster was observed around this structure, which caused asymmetrical microtubule distribution around the nuclear envelope before NEBD. Next, it was observed that TACC3 had over 29-fold greater expression than CCP110, CKAP5, and DISC1, and after being depleted using siRNA, there was complete disruption of the huoMTOC, and the distribution of microtubules was drastically diminished. The other 3 proteins showed similar but less severe diminishment of the huoMTOC when depleted. Next, to visualize the dynamic process of huoMTOC-regulated spindle assembly, 3D time-lapse imaging was used following NEBD. This showed the huoMTOC fragments and relocates on the kinetochores to initiate microtubule nucleation and spindle assembly. Again, each huoMTOC component was down-regulated in human oocytes and brought through this stage, showing that with each component there was significant impairment of spindle microtubule nucleation and spindle assembly compared with the control group (P &lt; 0.001), and spindle microtubules were greatly decreased. It was hypothesized that given the key role of the huoMTOC in human spindle assembly, a disrupted huoMTOC resulting from mutations in CCP110m CKAP5, DISC1, or TACC3 may cause abnormal oocyte maturation in patients. A cohort of 1394 infertile female patients characterized by oocyte maturation arrest was screened for mutations through whole-exome sequencing data sets. Two patients with loss-of-function mutations in TACC3 were identified, and analysis of their retrieved oocytes found a missing huoMTOC, suggesting the disruption of the huoMTOC impaired the nucleation of microtubules in the oocytes of patients. This study identified and characterized a structure, which was named the huoMTOC, which serves as a major site of microtubule nucleation and is required for spindle assembly in human oocytes.

Retracted: Study on the Influencing Mechanism of Human Chorionic Gonadotropin (hCG) on Oocyte Maturation in Patients with Polycystic Ovary Syndrome.

[This retracts the article DOI: 10.1155/2022/7933166.].

Study on the Influencing Mechanism of Human Chorionic Gonadotropin (hCG) on Oocyte Maturation in Patients with Polycystic Ovary Syndrome.

The study was aimed at investigating the influence of human chorionic gonadotropin (hCG) hormone on oocyte maturation in the patients with polycystic ovary syndrome (PCOS). A total of 54 patients with PCOS who received in vitro maturation (IVM) treatment in the Cheeloo College of Medicine, Shandong University, were divided into two groups: one group who underwent hCG injections was the observation group (OG; n = 27) and other was the control group (CG; n = 27) with no hCG injection. The oocyte development and the expression of steroid hormone synthesis-related genes including gonadotropin-releasing hormone receptor (GnRHR), Conexin43, epidermal growth factor-related genes, luteinizing hormone/choriogonadotropin receptor (LHCGR), epiregulin (EREG), and vascular endothelial growth factor (VEGF) were examined. The human ovarian granulosa cell line (SVOG cells) and ovarian epithelial cell line (HOSEpiC cells) were employed to analyze the effect of hCG on the biological behaviour of cells. As a result, OG showed higher normal fertilization, cleavage, and high-qualified embryo rate than CG. Expression levels of GnRHR, Cx43, LHCGR, EREG, and VEGF were significantly elevated in granulosa cells in the OG group. Western blot revealed that phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and rapamycin (mTOR) proteins were decreased in granulosa cells under hCG intervention. A biological behaviour test indicated that the multiplication capacity of hCG-intervened SVOG and HOSEpiC was increased, while the apoptosis was decreased. In conclusion, hCG could accelerate follicular development and oocyte maturation by activating oocyte maturation genes in PCOS patients, which could significantly improve and popularize the application of IVM technology.

VEGF Concentration in a Preovulatory Leading Follicle Relates to Ovarian Reserve and Oocyte Maturation during Ovarian Stimulation with GnRH Antagonist Protocol in In Vitro Fertilization Cycle.

Serum vascular endothelial growth factor (VEGF) is involved in follicular vascularization, oxygenation, and consequently in oocyte maturation and embryo development. Unanswered questions remain regarding the relationship of intrafollicular VEGF level in preovulatory leading follicles to oocyte maturation and ovarian reserve during ovarian stimulation. We conducted this study to investigate the relationship of intrafollicular VEGF level in the fluid of single preovulatory leading follicles to ovarian reserve and oocyte maturation in patients receiving GnRH antagonist in vitro fertilization (IVF) protocol treatment. One hundred and eighty-five patients receiving IVF treatment were recruited and assigned to low-, normal-, and high-ovarian-reserve groups according to their serum anti-Müllerian hormone (AMH) level. Follicular fluid (FF) in preovulatory leading follicles, serum profiles, and clinical variables were collected for analysis. The result disclosed a significant among-group difference in FF VEGF concentration. Moreover, the serum AMH level was also negatively correlated with FF VEGF level. The oocyte maturation rate tended to be increased at higher AMH levels. FF VEGF concentration was significantly positively correlated with basal FSH level. In conclusion, FF VEGF concentration has a negative association with ovarian reserve level and oocyte maturation rate in patients undergoing GnRH antagonist IVF protocols.

The impact of indomethacin on the number of oocytes retrieved and IVF outcomes in patients with poor ovarian response

ObjectiveThe aim of this retrospective case-control study was to analyze the effect of administering indomethacin after triggering final oocyte maturation in patients with poor ovarian response (POR) on the cycle cancellation rate due to premature ovulation (PO), the number of oocytes retrieved and the clinical outcomes of IVF cycles. Study DesignA total of 214 patients with POR, diagnosed according to the Bologna criteria, who underwent fresh IVF cycle via flexible gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol were enrolled in the study. The control group consisted of 100 patients, whereas the indomethacin group included 114 patients who received 100 mg rectal indomethacin administered twice within the same day (twelve hours apart) –starting at twelve hours after triggering. Cycle cancelation rates (CCR), number of oocytes retrieved (nOR), implantation rates (IR), biochemical pregnancy (BP) and clinical pregnancy loss rates (CPL), ongoing pregnancy rates (OPR) and live birth rates (LBR) were compared between the indomethacin and control groups. ResultsThe CCR rate was significantly lower in the indomethacin group (1.8%) compared to the control group (1.8% vs %12%, p = 0.01). In the control group, those with cycle cancellation were older than those without cycle cancellation (mean age 42.2 ± 2.3 years vs. 39.36 ± 4.3 years, p = 0.001) and had lower anti-Müllerian hormone levels and lower antral follicle count (0.59 ± 0.2 ng/mL vs 0.79 ± 0.2 ng/mL, p = 0.001 and 4 ± 0.6 vs 5.7 ± 1.7, p = 0.001, respectively). In multivariable analysis, when the dependent variable in the logistic regression model was coded as the absence of cycle cancellation, it was observed that only indomethacin had a statistically significant effect on cycle cancellation (β = −1.931, standard error = 0.832, Exp(B) = 0.145, p = 0.020). nOR was higher in the indomethacin group than control group but the difference did not reach significance (p = 0.07). Moreover, the IR, OPR and LBR, BP and CPL values were similar in the indomethacin and control groups (p > 0.05). ConclusionsBased on data from this study, it can be concluded that indomethacin reduces cycle cancelation due to PO in patients with POR –without compromising implantation and pregnancy rates. However, further randomized controlled trials with larger sample sizes are required to clarify the definitive effect of indomethacin in the treatment of patients with POR.

Outcome of in-vitro oocyte maturation in patients with PCOS: does phenotype have an impact?

Outcome of in-vitro oocyte maturation in patients with PCOS: does phenotype have an impact?

Association between body mass index and oocyte maturation in patients triggered with GnRH agonist who are at high risk for severe ovarian hyperstimulation syndrome: an observational cohort study.

Is body-mass index (BMI) associated with oocyte maturation in women at high risk for developing severe ovarian hyperstimulation syndrome (OHSS) who are triggered with gonadotrophin releasing hormone (GnRH) agonist? Prospective observational cohort study. A total of 113 patients at high risk for severe OHSS (presence of at least 19 follicles ≥11 mm) pre-treated with gonadotrophin releasing hormone (GnRH) antagonists and recombinant FSH were administered 0.2 mg triptorelin to trigger final oocyte maturation. Patients were classified in two groups depending on their BMI: ΒΜΙ less than 25 kg/m2 (n = 72) and ΒΜΙ 25 kg/m2 or over (n = 41). Baseline, ovarian stimulation and embryological characteristics, as well as luteal-phase hormone profiles, were compared in patients classified into the two BMI groups. The main outcome measure was the number of mature oocytes. A significantly higher number of mature (metaphase II) oocytes (19 [18-21] versus 16 [13-20], P = 0.029) was present in women with BMI less than 25 kg/m2 compared with those with BMI 25 kg/m2 or greater. The number of retrieved oocytes, the number of fertilized oocytes, oocyte retrieval, maturation and fertilization rates were similar in the two groups. A significantly higher dose of recombinant FSH was required for patients with BMI 25 kg/m2 or greater compared with patients with BMI less than 25 kg/m2 (1875 [1650-2150] IU versus 1650 [1600-1750] IU, P = 0.003) and the two groups displayed different luteal phase hormonal profiles. Among women at high risk for developing severe OHSS who are triggered with a standard dose (0.2 mg) of the GnRH agonist triptorelin, women with BMI 25 kg/m2 or greater had significantly fewer mature oocytes, required a higher total dose of recombinant FSH compared with women with BMI less than 25 kg/m2.

Is oocyte maturation rate associated with triptorelin dose used for triggering final oocyte maturation in patients at high risk for severe ovarian hyperstimulation syndrome?

Are oocyte maturation rates different among 0.1, 0.2 and 0.4mg triptorelin used for triggering final oocyte maturation in patients at high risk for ovarian hyperstimulation syndrome (OHSS) undergoing ICSI? A dose of 0.1mg triptorelin results in similar oocyte maturation rates compared to higher doses of 0.2 and 0.4mg in patients at high risk for OHSS undergoing ICSI. The GnRH agonist triptorelin is widely used instead of hCG for triggering final oocyte maturation, in order to eliminate the risk of severe OHSS in patients undergoing ovarian stimulation for IVF/ICSI. However, limited data are currently available regarding its optimal dose use for this purpose in patients at high risk for OHSS. A retrospective study was performed between November 2015 and July 2017 in 131 infertile patients at high risk for severe OHSS undergoing ovarian stimulation for ICSI. High risk for severe OHSS was defined as the presence of at least 19 follicles ≥11mm in diameter on the day of triggering final oocyte maturation. Ovarian stimulation was performed with recombinant FSH and GnRH antagonists. Patients received 0.1 (n = 42), 0.2 (n = 46) or 0.4mg (n = 43) triptorelin for triggering final oocyte maturation. Hormonal evaluation of FSH, LH, estradiol (E2) and progesterone (PRG) was carried out on the day of triggering final oocyte maturation, 8 and 36hours post triggering and 3, 5, 7, and 10days after triptorelin administration. During this period, all patients were assessed for symptoms and signs indicative of severe OHSS development. Primary outcome measure was oocyte maturation rate, defined as the number of metaphase II (MII) oocytes divided by the number of cumulus-oocyte-complexes retrieved per patient. Results are expressed as median (interquartile range). No significant differences in patient baseline characteristics were observed among the 0.1mg, the 0.2mg and the 0.4mg groups. Regarding the primary outcome measure, no differences were observed in oocyte maturation rate among the three groups compared [82.6% (17.8%) versus 83.3% (18.8%) versus 85.1% (17.2%), respectively, P = 0.686].In addition, no significant differences were present among the 0.1mg, 0.2mg and 0.4mg groups, regarding the number of mature (MII) oocytes [21 (13) versus 20 (6) versus 20 (11), respectively; P = 0.582], the number of oocytes retrieved [25.5 (13) versus 24.5 (11) versus 23 (12), respectively; P = 0.452], oocyte retrieval rate [81.0% (17.7%) versus 76.5% (23.5%) versus 75.0% (22.5), respectively; P = 0.088], the number of fertilized (two pronuclei) oocytes [12.5 (9) versus 14.5 (7) versus 14.0 (8), respectively; P = 0.985], fertilization rate [71.7% (22%) versus 77.1% (19.1%) versus 76.6% (23.3%), respectively; P = 0.525] and duration of luteal phase [7 (1) versus 8 (2) versus 7 (1) days, respectively; P = 0.632]. Moreover, no significant differences were present among the three triptorelin groups regarding serum levels of LH, FSH, E2 and PRG at any of the time points assessed following triggering of final oocyte maturation. This is a retrospective study, and although there were no differences in the baseline characteristics of the three groups compared, the presence of bias cannot be excluded. Based on the results of the current study, it appears that triggering final oocyte maturation with a lower (0.1mg) or a higher dose (0.4mg) of triptorelin, as compared to the most commonly used dose of 0.2mg, does not confer any benefit in terms of oocyte maturation rate in patients at high risk for severe OHSS. No external funding was obtained for this study. There are no conflicts of interest.

Psychological and oxidative stress induce apoptosis through TRPV1 channel activation in granulosa cells of oocyte during in vitro fertilization

Several physiological and pathophysiological functions such as mitochondria and phagocytosis induce oxidative stress. Oxidative stress results in excessive production of reactive oxygen species (ROS). There is a high amount of psychologically and chemically stress in in vitro fertilization (IVF), because of presence stressful permanent infertility and treatment procedures (An et al. 2013). Oocytes are surrounded by granulosa cells. It is well-known that there is a direct relationship between oxidative stress contents of granulosa cells and oocyte quality (Tola et al 2013). Excessive Ca2+ influx induces excessive mitochondrial ROS production and apoptosis through activation of caspase activations. Involvement of voltage gated Ca2+ channels on oocyte quality and apoptosis in the granulosa cells has been clarified by results of several studies (Platano et al. 2013; Tola et al 2013). Transient receptor potential vanilloid 1 (TRPV1) channel is a calcium permeable and non-selective cation channel. The similar effects of voltage gated calcium channels may present between oxidative stress and TRPV1 channel activation in the oocyte, because the TRPV1 channel is activated by excessive production of ROS. The importance of TRPV1 channel on the oocyte maturation was recently reported (Cecconi et al. 2019).&amp;nbsp; In the oral presentation, I will review recent studies on apoptosis through TRPV1 channel activation in granulosa cells of oocyte during IVF.&amp;nbsp; In conclusion, current literature data indicated that&amp;nbsp;psychological and oxidative stress-induced ROS, apoptosis and Ca2+ contents of oocyte and granulosa cells have very important roles on the oocyte maturation in patients with infertility during the IVF. There are some involvement clues of TRPV1 channels on the oocyte maturation and apoptosis, but the subject needs future studies.&amp;nbsp;

GNRH agonist versus HCG to induce final oocyte maturation in patients at low risk of OHSS

Ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol offers the flexibility of utilizing a GnRH agonist (GnRHa) or hCG trigger for final oocyte maturation. When the follicle number or estradiol (E2) concentration is low, an hCG trigger may be selected if it is determined that the patient is at low risk of ovarian hyperstimulation syndrome (OHSS). It is unclear whether a GnRHa or hCG trigger in this clinical scenario yields superior outcomes.

Gonadotropin-releasing hormone agonist triggering of oocyte maturation in assisted reproductive technology cycles.

Gonadotropin-releasing hormone agonists (GnRHa) have gained increasing attention in the last decade as an alternative trigger for oocyte maturation in patients at high risk for ovarian hyperstimulation syndrome (OHSS). They provide a short luteinizing hormone (LH) peak that limits the production of vascular endothelial growth factor, which is the key mediator leading to increased vascular permeability, the hallmark of OHSS. Initial studies showed similar oocyte yield and embryo quality compared with conventional human chorionic gonadotropin (hCG) triggering; however, lower pregnancy rates and higher miscarriage rates were alarming in GnRHa triggered groups. Therefore, two approaches have been implemented to rescue the luteal phase in fresh transfers. Intensive luteal phase support (iLPS) involves administiration of high doses of progesterone and estrogen and active patient monitoring. iLPS has been shown to provide satisfactory fertilization and clinical pregnancy rates, and to be especially useful in patients with high endogenous LH levels, such as in polycystic ovary syndrome. The other method for luteal phase rescue is low-dose hCG administiration 35 hours after GnRHa trigger. Likewise, this method results in statistically similar ongoing pregnancy rates (although slightly lower than) to those of hCG triggered cycles. GnRHa triggering decreased OHSS rates dramatically, however, none of the rescue methods prevent OHSS totally. Cases were reported even in patients who underwent cryopreservation and did not receive hCG. GnRH triggering induces a follicle stimulating hormone (FSH) surge, similar to natural cycles. Its possible benefits have been investigated and dual triggering, GnRHa trigger accompanied by a simultaneous low-dose hCG injection, has produced promising results that urge further exploration. Last of all, GnRHa triggering is useful in fertility preservation cycles in patients with hormone sensitive tumors. In conclusion, GnRHa triggering accompanied by appropriate luteal phase rescue protocols is a relatively safe option for patients at high risk for OHSS.

Reproducibility and clinical significance of pre-ovulatory serum progesterone level and progesterone/estradiol ratio on the day of human chorionic gonadotropin administration in infertile women undergoing repeated in vitro fertilization cycles

BackgroundThe objective of this study was to explore the cycle-to-cycle reproducibility of serum progesterone level and progesterone/estradiol (P/E2) ratio in the final step of triggering oocyte maturation in patients undergoing repeated consecutive controlled ovarian hyperstimulation for in vitro fertilization (COH-IVF) treatment and to investigate the clinical parameters associated with serum progesterone concentration and P/E2 ratio.MethodsWe retrospectively studied 524 cycles in 203 infertile women who underwent two or more fresh COH-IVF cycles from July 1998 to May 2012 in a university hospital IVF unit. The patients were divided into groups according to the number (2, 3 or > = 4) of total successive IVF cycles with successful oocyte retrieval. The within-subject reproducibility of serum P and P/E2 was tested by calculating intra-class correlation coefficients (ICCs). Multiple linear regression analysis was used to assess the association between patient variables and pre-ovulatory serum P level and P/E2 ratio.ResultsThe ICCs in women who underwent 2, 3 and > = 4 IVF cycles were −0.052, 0.163 and 0.212, respectively, for serum P concentration and 0.180, 0.168 and 0.148, respectively, for P/E2 ratio. All ICCs for both serum P and P/E2 ratio were indicative of poor reproducibility. The number of oocytes was significantly positively related to P concentration, and endometrial thickness was significantly negatively related to P concentration and P/E2 ratio.ConclusionThe cycle-to-cycle reproducibility of pre-ovulatory serum P concentration and P/E2 ratio was poor in individual patients, and these fluctuations were more cycle- than patient-dependent. The number of oocytes was the most significant factor relating to P concentration. By using milder stimulation approach to produce fewer oocytes in the next cycle is a strategy to overcome the high serum P concentration, while clinicians should consider each patient’s general condition including the age, ovarian reserve, embryo grading and the capacity of frozen-thawed embryo transfer.

Maternal and neonatal outcomes after gonadotropin-releasing hormone agonist trigger for final oocyte maturation in patients undergoing in vitro fertilization

To compare the rate of congenital anomalies, obstetrical complications, and neonatal complications in antagonist cycles where either GnRH agonist (GnRHa) or hCG was used for final oocyte maturation. Retrospective cohort study. University-based tertiary fertility center. Three hundred ninety-two women under 40years of age who underwent controlled ovarian stimulation using a GnRH antagonist protocol and who had final oocyte maturation triggered with either a GnRHa or hCG that resulted in pregnancy and delivery after 16weeks' gestation. GnRHa versus hCG trigger of final oocyte maturation. Congenital anomaly rates, obstetrical complications, and neonatal complications. There were no significant differences in the rate of congenital anomalies between GnRHa and hCG trigger (6.6 vs. 9.2%). There were also no differences in the maternal complications (27.6 vs. 20.8%) or neonatal complications (19.7 vs. 20.0%) between the GnRHa trigger and hCG trigger groups. GnRHa trigger does not affect the rate of congenital anomalies or obstetrical or neonatal complications and remains a viable option in the prevention of ovarian hyperstimulation syndrome.

Delaying the oocyte maturation trigger by one day leads to a higher metaphase II oocyte yield in IVF/ICSI: a randomised controlled trial.

BackgroundThe negative impact of rising progesterone levels on pregnancy rates is well known, but data on mature oocyte yield are conflicting. We examined whether delaying the oocyte maturation trigger in IVF/ICSI affected the number of mature oocytes and investigated the potential influence of serum progesterone levels in this process.MethodsBetween January 31, 2011, and December 31, 2011, 262 consecutive patients were monitored using ultrasound plus hormonal evaluation. Those with > =3 follicles with a mean diameter of > =18 mm were divided into 2 groups depending on their serum progesterone levels. In cases with a progesterone level < = 1 ng/ml, which was observed in 59 patients, 30-50% of their total number of follicles (only counting those larger than 10 mm) were at least 18 mm in diameter. These patients were randomised into 2 groups: in one group, final oocyte maturation was triggered the same day; for the other, maturation was triggered 24 hours later. Seventy-two patients with progesterone levels > 1 ng/ml were randomised in the same manner, irrespective of the percentage of larger follicles (> = 18 mm). The number of metaphase II oocytes was our primary outcome variable. Because some patients were included more than once, correction for duplicate patients was performed.ResultsIn the study arm with low progesterone (<= 1 ng/ml), the mean number of metaphase II oocytes (+/-SD) was 10.29 (+/-6.35) in the group with delayed administration of the oocyte maturation trigger versus 7.64 (+/-3.26) in the control group. After adjusting for age, the mean difference was 2.41 (95% CI: 0.22-4.61; p = 0.031). In the study arm with elevated progesterone (>1 ng/ml), the mean numbers of metaphase II oocytes (+/-SD) were 11.81 (+/-9.91) and 12.03 (+/-7.09) for the delayed and control groups, respectively. After adjusting for PCOS (polycystic ovary syndrome) and female pathology, the mean difference was -0.44 (95% CI: -3.65-2.78; p = 0.79).ConclusionsDelaying oocyte maturation in patients with low progesterone levels yields greater numbers of mature oocytes.Trial registrationB67020108975 (Belgian registration) and NCT01980563 (ClinicalTrials.gov).

Repeated injection of GnRH agonist for triggering final oocyte maturation in patients at high risk of OHSS in GnRH antagonist protocol: a prospective, cohort study

Gonadotropin-releasing hormone (GnRH) agonist is sufficient for triggering final oocyte maturation in GnRH antagonist protocol and can significantly reduce incidence of ovarian hyperstimulation syndrome(OHSS) in high-risk patients. However, lower oocyte yield was reported in patients with lower LH level post trigger with single injection of GnRH agonist, which might be related to the shorter duration and lower amount of LH induced by GnRH agonist. Our aim is to study repeated injection of GnRH agonist for preventing OHSS and maintain clinical outcome in high risk patients who receive controlled ovarian stimulation (COS) in GnRH antagonist protocol.

Modified luteal support following GnRH-agonist trigger

To demonstrate the use of modified luteal support following GnRh-agonist trigger in patients undergoing IVF/ICSI and at risk of Ovarian Hyper Stimulation Syndrome [OHSS] in preventing early OHSS without compromising pregnancy rate. This prospective, observational study was carried out on 49 patients undergoing IVF/ICSI and at risk of OHSS at Nova IVI Fertility, Ahmedabad from January 2012 to December 2012. The patients aged between 26 and 34 years [average 31 years], underwent stimulation from second day of period with 100 to 300IU of Gonadotropins[average 200IU] using the flexible antagonist protocol. GnRH agonist,[Triptorelin 0.2mg] was given to induce final oocyte maturation in patients at risk of developing OHSS[>20 follicles of >16 mm on the day of trigger].Average estradiol on the day of trigger was 5353+3983 pg/ml. Transvaginal oocyte retrieval[OR]was performed 35hours after the trigger. Luteal phase support was provided in form of vaginal progesterone tablets(200mg 3times/day) and oral estradiol valerate(2mg twice/day)from day after OR. Patients also received 1500 I.U. of recombinant hCG on day of ET. 2embryos were transferred on day3 after OR. An average 22.7+5.6 oocytes were retrieved,76% of which were at metaphaseII. Fertilization rate was 81% and 14+5 embryos were obtained. 2embryos were transferred on day3 in 42 patients and positive hCG rate was 30.9%[13/42] per ET. There was no early OHSS;one patient developed late onset pregnancy induced severe OHSS. Implantation rate was 19%[16/84], rates of miscarriage, ectopic and twins were 7.6%, 15.3%, 23% & ongoing pregnancy rate at 10 weeks was 23.8% [10/42]. GnRH agonists can be used effectively as an alternative to hCG trigger in patients at high risk of OHSS. This delayed administration of hCG provides luteal support& gives time to assess the number & grade of embryos & decide whether the patient should be given hCG & have an ET or should have elective cryopreservation of all embryos.

Maternal and neonatal outcomes after GnRH-AGONIST trigger for final oocyte maturation in patients undergoing in vitro fertilization (IVF)

Induction of oocyte maturation with GnRHa has been shown to be effective in the prevention of ovarian hyperstimulation syndrome (OHSS). However, there are no studies evaluating its effect on maternal or neonatal outcomes. The aim of this study was to evaluate the maternal obstetrical antepartum, intrapartum, and postpartum complications, neonatal complications, and congenital anomalies in patients undergoing IVF using a GnRH-antagonist protocol where GnRH-agonist was used for final oocyte maturation.

Triggering final oocyte maturation with gnrh agonist in patients with polycystic ovaries undergoing IVF

To assess the safety and efficacy of gonadotropin releasing hormone (GnRH) agonist administration for triggering final oocyte maturation in patients with polycystic ovaries (PCO) at high risk for ovarian hyperstimulation syndrome (OHSS).