Gn Stimulation Research Articles

Gonadotropin-Releasing Hormone (GnRH) Agonist Protocol Improves Pregnancy Outcomes During In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) Treatment in Young Infertile Women: A Retrospective Study.

Objective The objective of this study was to determine if gonadotropin-releasing hormoneagonist (GnRH-a) orgonadotropin-releasing hormoneantagonist (GnRH-ant) protocols during in vitrofertilization (IVF) or intracytoplasmic sperm injection (ICSI)treatment in younginfertile women improvetheir pregnancy outcomes. Methodology We retrospectively reviewed the records of 876young infertile women aged 20-35 years who underwentfresh embryo transfer in IVF/ICSI cycles.The data were collected from their initial visits to the reproductive medicine center ofthe Second Affiliated Hospital of Zhengzhou University between January 2019 and December 2022. We divided them into two groups according to the controlled ovarian hyperstimulation (COH) protocols: GnRH-a (n = 580) and GnRH-ant (n = 296).The primary outcome assessed in this study was the live birth rate. The secondary observation indicators included the total dose and duration of gonadotropin (Gn),total embryo transfer,day three (D3) embryo transfer, total two pro-nuclei (2PN) cleavage count, number of fertilizations, and implantation rate. Results The live birth rate had no clinical significance (P> 0.05). The total dose and duration of Gn stimulation in the GnRH-ant group were lower than in the GnRH-a group (P < 0.05). The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer, and mature oocytes in metaphase II (MII) of D3 embryos in the GnRH-a group were higher than those in the GnRH-ant group (P < 0.05). The clinical pregnancy rate and implantation rate of the GnRH-a group were higher than those of the control group. Conclusions The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer and MII of D3 embryos, clinical pregnancy, and implantation rateswere significantly higher in the GnRH-a protocol group.The total dosage of Gn and duration of Gn stimulation were lower in the GnRH-ant group than in the GnRH-a group. These findings provide the basis for the selection of the COH protocol in normal Chinese ovarian response patients undergoing IVF/ICSI.

Effect of growth hormone administration on ameliorating pregnancy outcome in women with advanced maternal age and exploration of its optimized utilization.

Age-related fertility decay is a great challenge for clinicians. Growth hormone (GH) supplementation has been studied as an adjuvant since late 1980s. However, it has not come to a consensus on the GH administration due to the ambiguous efficacy among studies with different enrolled population and dosage regime. A self-controlled retrospective study was conducted on women with advanced maternal age who underwent at least a previous cycle without GH (GH-) and a subsequent cycle with GH co-treatment (GH+). The ovarian stimulation parameters and outcomes were compared between the two cycles and logistical analysis was applied to further explore the association between GH administration protocol as well as other clinical parameters and cumulative live birth in GH+cycle. A total of 150 women aged 35-43 were included. The number of oocytes retrieved, MII oocytes, 2PNs, transferrable embryos and good-quality embryos in GH+ significantly increased (p < 0.001). The proportion of cycles with no transferrable embryos was significantly reduced in GH+ cycle compared with previous GH- cycle (3 vs. 32; p < 0.001). GH co-treatment cycles showed significantly higher clinical pregnancy rates (43.75% vs. 6.06%; 38.35% vs. 12.04%, p < 0.001), live birth rates (29.17% vs. 0; 27.07% vs. 0, p < 0.001) in both fresh and frozen-thawed embryo transfer cycle. Cumulative live birth rate of the GH+ cycle reached 33.33%. Use of GH prior to Gn stimulation and lasting until the hCG day seemed to achieve a higher successful live birth rate (OR 2.312, 95%CI 1.074-5.163, p=0.032). GH supplementation could ameliorate pregnancy outcome in women with advanced maternal age. Dosage regimen of long-term pretreatment prior to Gn stimulation (4 IU every other day) and 4 IU per day until hCG day may of greater efficacy compared with concurrent administration with Gn. Additionally, it's worthy of exploring whether an individualized dosage regimen based on the IGF or IGFBP level of patient would be more reasonable and effective. More well-designed prospective trials with large sample size and fundamental experiments on the mechanism are required to testify findings above.

Comparison of Pregnancy Outcomes in Thyroid Antibody-Positive Women with Different Fertilization Methods

<i>Objective</i> To compare the pregnancy outcomes of thyroid antibody (ATA) positive women treated by different fertilization methods during in vitro fertilization-embryo transfer. Methods A total of 204 female patients with normal thyroid function and positive ATA in the reproductive Medicine Center of the First Hospital of Shanxi Medical University from January 2020 to January 2022 were selected. According to different fertilization methods, they were divided into IVF group and ICSI group, including 115 IVF cycles and 89 ICSI cycles. The general data, clinical indicators after ovulation induction, fertilization, embryo status, and pregnancy outcome of the two groups were compared. <i>Results</i> There were no significant differences in age, BMI, bE₂, FSH, FT₃, FT₄, AFC, Gn dosage, Gn stimulation time, E₂ on HCG day, P on HCG day, intrauterine thickness on HCG day, number of retrieved oocytes and average number of embryos transferred between the two groups (P>0.05). The fertilization rate of the ICSI group was higher than that of IVF group within the group, while the high-quality embryo rate was significantly lower than that of the IVF group, with statistical significance (P<0.05). There were significant differences in sperm motility and sperm density between the two groups (P<0.05), and there was no significant difference between sperm volume and normal morphology rate (P>0.05). There were no significant differences in embryo implantation rate, biochemical pregnancy rate, clinical pregnancy rate, early abortion rate and live birth rate between the two groups (P>0.05). Logistic regression analysis showed that the method of assisted pregnancy and semen quality were not independent factors affecting high-quality embryo (P>0.05). In IVF group, TGAb was negatively correlated with fertilization rate (r=-0.202, P<0.05); and in ICSI group, TPOAb was negatively correlated with high quality embryo rate (r=-0.349, P<0.05). <i>Conclusion</i> Thyroid autoimmunity (TAI) in infertile women undergoing assisted reproductive technology (ART), the semen quality should be considered as the priority criteria for ATA. ICSI should not be recommended as routine fertilization.

Effect of weight loss on pregnancy outcomes, neuronal-reproductive-metabolic hormones and gene expression profiles in granulosa cells in obese infertile PCOS patients undergoing IVF-ET.

ObjectiveTo investigate the effect of weight loss on pregnancy outcomes, PCOS related neuronal-reproductive-metabolic hormones and ovarian granulosa cell gene expression profiles in obese PCOS infertile patients undergoing in vitro fertilization-embryo transfer (IVF-ET).Methods75 patients undergoing IVF-ET due to tubal factors alone collected as the control group (group A), and 352 patients with obese PCOS infertility were divided into four groups according to the amount of weight loss before IVF: 0 kg (group B), 1-5 kg (group C), 5-10 kg (group D), and >10 kg (group E). Six cases of ovarian granulosa cells were collected randomly with the random number table method in each group for detecting mRNA profiling. Pathway networks and biological functions of the differentially expressed genes were analyzed. Validation by RT-PCR was performed.Results(1) The levels of luteinizing hormone(LH), testosterone(T) and homeostasis model assessment insulin resistance(HOMA-IR) in group E were significantly lower than those in groups B and C (P<0.05). (2) Compared with groups A and E, groups B and C showed increased total gonadotropin (Gn) and days of Gn stimulation (P<0.05), and the E2 level on trigger day and number of oocytes obtained in group B was significantly less than that in group E (P<0.05 or 0.01). Embryo implantation rate, clinical pregnancy rate and live birth rate were increased and miscarriage rate was decreased in groups A, D and E compared with group B (P<0.05 or 0.01). (3) There were significant differences among the control group and PCOS groups in some genes that are involved in neuronal-reproductive-metabolic endocrine, transcriptional regulation, cell proliferation and differentiation, etc (P<0.05). RNA-Seq results were validated by real time PCR analysis for the expression of follicle stimulating hormone receptor (FSHR), drosophila mothers against decapentaplegic protein 7(Smad7) and glutathione peroxidase 3(GPX3) genes that are known to have an important role in follicular development. Functional alterations were confirmed by the improvement in the ovarian responsiveness to Gn and embryo quality.ConclusionWeight loss more than 5kg may regulate the neuroreproductive endocrine hormone secretion, insulin resistance and gene expression profiles of ovarian granulosa cells, so as to improve the ovarian responsiveness to Gn, the embryo quality, embryo implantation rate, clinical pregnancy rate, live birth rate, and reduce the spontaneous abortion rate in obese infertile PCOS patients undergoing IVF-ET.Clinical trial registration www.chictr.org.cn, identifier ChiCTR1800018298.

Effects of Acupuncture on Endometrium and Pregnancy Outcomes in Patients with Polycystic Ovarian Syndrome Undergoing in vitro Fertilization-Embryo Transfer: A Randomized Clinical Trial.

To observe the effect of acupuncture on endometrium and pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) infertility undergoing in vitro fertilization-embryo transfer (IVF-ET). Eighty-three patients were randomly assigned to observation group (40 cases) and control group (43 cases) according to the random numbers generated by SPSS software. The patients of the two groups received GnRH agonist long protocol as a routine treatment. In the observation group, acupuncture was given at two acupoint groups for 30 min once every other day. Group 1 included Guanyuan (CV 4), Qihai (CV 6), Zhongji (CV 3), bilateral acupoints Zigong (EX-CA1). Group 2 included Mingmen (GV 4), Yaoyangguan (GV 3), bilateral Shenshu (BL 23) and Ciliao (BL 32). The two groups of acupoints were used alternately. The whole needling process was performed at the time of ovulation induction until the transplantation day and consisted of 3 courses, while the control group did not receive acupuncture interventions. The Gn dosage and Gn stimulation time, endometrial thickness and type (A, B, and C), serum oestradiol (E2) and progesterone (P) levels on the day of injection of human chorionic gonadotropin (hCG), clinical pregnancy rate, as well as live birth rate were observed. Adverse reactions were also be recorded. All patients were followed up for the pregnant rate 14 days after IVF-ET and live birth rate after pregnancy. All adverse reactions (AEs) of acupuncture were recorded during the trial. The Gn dosage and Gn stimulation time in the observation group were lower in the observation group than in the control group (P<0.01). The proportion of type A endometrium in the observation group were higher than that in the control group (P<0.05). The serum E2 and P levels on the day of hCG injection was lower and the clinical pregnancy rate was higher in the observation group compared to those in the control group (P<0.05). There was no serious AEs during this trial. Acupuncture can improve the proportion of type A endometrium, regulate the levels of serum E2 and P on the day of hCG injection, and improve the pregnancy rate in patients with PCOS infertility undergoing IVF-ET.

Comparison of clinical outcomes between the depot gonadotrophin-releasing hormone agonist protocol and gonadotrophin-releasing hormone antagonist protocol in normal ovarian responders

BackgroundThe gonadotrophin-releasing hormone (GnRH) antagonist protocol has some advantages, such as a simple method, short medication duration, and low incidence of ovarian hyperstimulation syndrome, but whether the GnRH antagonist protocol is suitable for normal ovarian responders has been controversial. We compared the clinical outcomes of fresh and frozen-thawed transfer cycles between the depot GnRH agonist protocol and GnRH antagonist protocol in normal ovarian responders.MethodsData of normal ovarian responders who underwent in vitro fertilization-embryo transfer (IVF-ET) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) between January 2017 and December 2018 in our hospital were retrospectively analysed. In this study, there were 1119 fresh transfer cycles, including 502 GnRH antagonist cycles (GnRH antagonist group) and 617 depot GnRH agonist cycles (depot GnRH agonist group), as well as 468 frozen-thawed transfer cycles, includng 191 GnRH antagonist cycles (GnRH antagonist group) and 277 depot GnRH agonist cycles (depot GnRH agonist group). The clinical outcomes were compared between the GnRH antagonist group and the depot GnRH agonist group.ResultsWith the fresh transfer cycles, there were no statistically significant differences in the anti-Mullerian hormone level, number of transferred embryos or high-quality embryo rate between the two groups. The total dosage of gonadotropin (Gn), duration of Gn stimulation, number of oocytes retrieved, clinical pregnancy rate and incidences of moderate and severe ovarian hyperstimulation syndrome (OHSS) were significantly lower but the abortion rate was significantly higher in the GnRH antagonist group than in the depot GnRH agonist group (all P < 0.05). With the frozen-thawed transfer cycles, there were no statistically significant differences in the number of transferred embryos, clinical pregnancy rate or abortion rate between the two groups (all P > 0.05).ConclusionsWith the fresh transfer cycles, the GnRH antagonist protocol had a lower clinical pregnancy rate and lower incidences of moderate and severe OHSS than the depot GnRH agonist protocol, but with the frozen-thawed transfer cycles, both protocols had similar clinical pregnancy rates. These results remain to be further confirmed through large-sample, prospective, randomized and controlled studies.

The Predictive Value of the Follicular Output Rate on Pregnancy Outcome of Patients with Polycystic Ovary Syndrome Undergoing In Vitro Fertilization and Embryo Transfer.

BackgroundThis retrospective study aimed to evaluate the predictive value of the follicular output rate (FORT) on the pregnancy outcome of patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET).Material/MethodsBetween January 2012 and June 2016, a total of 1,541 patients with PCOS who underwent IVF-ET at our center were enrolled in the study. FORT was calculated as the pre-ovulatory follicle count (PFC)/antral follicle count (AFC)×100%.ResultsAccording to the FORT, patients were divided into low, medium, and high FORT groups. With an increase in the FORT, the PFC and serum estradiol at the day of human chorionic gonadotropin (hCG) injection, the number of retrieved oocytes, metaphase II (MII) oocytes, total number of embryos, and number of high-quality embryos significantly increased (P<0.05 and P<0.001) from the low to high FORT groups, while the AFC, gonadotropin (Gn) stimulation day, and total Gn decreased significantly (P<0.001). The live birth rate from frozen embryo transfer and the cumulative live birth rate was the lowest in middle FORT group but increased significantly in high FORT group (P<0.05). The correlation analysis between FORT and related factors showed that the FORT was negatively correlated with body mass index (BMI), Gn stimulation days, and total Gn (P<0.05).ConclusionsFORT is a powerful tool for measuring ovarian reactivity. For patients with PCOS, a high FORT to obtain high-quality embryos and perform frozen embryo transplantation can achieve good pregnancy outcome.

OR31-05 Emergence of Ovarian Hyperandrogenism and Luteal Insufficiency Following ESR1 Knockdown in the Mediobasal Hypothalamus of Adult Female Rhesus Monkeys

Diminished estradiol (E2) negative feedback action by neuronal ESR1 in the arcuate nucleus (ARC) of the mediobasal hypothalamus (MBH) is hypothesized to cause gonadotropin-releasing hormone (GnRH) hypersecretion, and thus LH excess, contributing to ovarian hyperandrogenism in polycystic ovary syndrome (PCOS). In primates, including humans, however, the mediating estrogen receptor is unknown. Thus, to test the hypothesis that diminished E2 action on ARC ESR1 contributes to female primate ovarian hyperandrogenism, eleven, ovary intact, adult female rhesus macaques, pair housed with female peers, received five 12µl MRI-guided MBH infusions into the rostral-to-caudal extent of both right and left ARC. Each infusion comprised gadolinium contrast agent and ~3-4 x 1010 adeno-associated virus 8 (AAV8) particles containing either a shRNA specific for ESR1 (n=6, ERaKD) or scrambled shRNA (n=5, control). Mid-surgery MRI scans identified targeting accuracy. 2-2.5 years following AAV8 infusion, EIA-determined P4 values were obtained from twice weekly serum samples; samples obtained during the follicular phase of menstrual cycles or anovulatory periods were submitted to liquid chromatography, tandem mass spectrometry (LCMS) for additional steroid hormones. LCMS-determined values were also obtained 0 hours (h) and 24 h following an IM injection of 200IU hCG. Both ERaKD (28.5 ± 1.3 days, mean ± SEM) and control (34.0 ± 3.3 days) female groups exhibited comparably regular menstrual cycles. ERaKD exhibited higher circulating levels of LH (2.8 ± 0.2 ng/ml, p=0.03), androstenedione (A4, 0.43 ± 0.03 ng/ml, p=0.03) and testosterone (T, 0.23 ± 0.03 ng/ml, p=0.09), and LH/FSH ratio (1.7 ± 0.2, p=0.05) compared to controls (LH, 2.1 ± 0.4; A4, 0.30 ± 0.05; T, 0.18 ± 0.01 ng/ml; LH/FSH 1.3 ± 0.2). Following an ovarian androgen-stimulating hCG injection, ERaKD 24-h peak levels for T (0.28 ± 0.01 ng/ml) were higher (p=0.03) compared to controls (0.21 ± 0.01 ng/ml). In addition, luteal insufficiency emerged in ERaKD females, with mean (2.4 ± 0.3 ng/ml), peak (3.6 ± 0.4 ng/ml) and area-under-the-curve (AUC, 23.2 ± 4.2 ng/ml/days) P4 values diminished compared to controls (mean, 3.6 ± 0.1, p=0.01; peak 5.7 ± 0.1 ng/ml, p=0.01; AUC, 43.7 ± 6.7 ng/ml/days, p=0.03). Taken together, these results suggest that knockdown of ARC ESR1 disrupts Gn stimulation of ovarian function, contributing to female monkey ovarian hyperandrogenism and menstrual cycle impairment emulating PCOS in women.

Mild stimulation protocol vs conventional controlled ovarian stimulation protocol in poor ovarian response patients: a prospective randomized controlled trial

To compare the efficacy of mild ovarian stimulation protocol and conventional controlled ovarian stimulation (COS) protocol for poor ovarian response (POR) patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). This single-center prospective randomized controlled trial conducted from September 2013 to September 2015, including 191 patients who met the Bologna criteria of POR. Ninety-seven patients allocated to the mild ovarian stimulation group (MS group) were stimulated according to the letrozole/antagonist protocol, while 94 patients in the controlled ovarian stimulation group (COS group) were stimulated according to a high dose of gonadotropin (Gn) combined with gonadotropin-releasing hormone agonist (GnRH-a) stop protocol. The cumulative live birth rate was the primary outcome. Chinese clinical trial number ChiCTR-TRC-13003454. Comparing with the COS group, both the stimulation duration and the total gonadotropin dose were significantly shorter and lower in the MS group (P < 0.001). A higher number of retrieved oocytes (P = 0.003) and transferrable embryos (P = 0.029) were obtained in the COS group. The cumulative live birth rates (OR 1.103; 95% CI 0.53 to 2.28; P = 0.791) were comparable between the two groups. The increase of Gn dose during ovulation stimulation was associated with a higher number of transferrable embryos for POR patients, but this increase did not lead to a concomitant improvement of reproductive outcome, especially in terms of the cumulative live birth rate. Using a mild stimulation protocol was economically preferential while it was as effective as higher doses of Gn stimulation protocol in reproductive outcome for POR patients.

Optimizing gonadotropin stimulation to maximize the likelihood of obtaining euploid embryos

In order to optimize the number of viable oocytes retrieved for IVF, reproductive endocrinologists alter gonadotropin (Gn) dosage and duration of simulation. The ultimate measure of a successful IVF cycle is a euploid embryo. Here we aimed to understand the relationship between commonly adjusted Gn stimulation parameters and the likelihood of obtaining euploid embryos. These insights better enable data-driven personalization of protocols for patients undergoing fertility treatments.

Clinical applications of different doses of leuprorelin acetate in in vitro fertilization-embryo transfer

To evaluate the clinical effect of different doses of leuprorelin acetate in in vitro fertilization-embryo transfer (IVF-ET). From January 2011 to December 2011, the data of 268 patients undergoing IVF and(or) intracytoplasmic sperm injection (ICSI) in Reproductive Medical Center, Clinical College of PLA, Anhui Medical University were studied retrospectively. All the patients were divided into three groups based on with long protocol and controlled ovarian stimulation (COH) including 83 cycles with 1.25 mg of leuprorelin in low dose group, 68 cycles with 1.88 mg of leuprorelin in high dose group, 117 cycles with 1.25 mg of diphereline in control group. The serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E(2)) and progesterone (P) before gonadotropin (Gn) administration on the days 3-5 of the menstrual cycle and on the day of hCG administration were detected, the dose and duration of Gn, number of oocytes retrieved, number of mature oocytes, the rates of fertilization, embryo cleaved, good-quality embryos clinical pregnancy and early miscarriage were compared among three groups. There were no significant differences in age, the level of LH and P on the day of hCG administration among three groups (P > 0.05). The level of FSH was (3.8 ± 1.6) U/L in low dose leuprorelin group, (3.1 ± 1.4) U/L in high dose of leuprorelin group and (2.4 ± 1.3) U/L in diphereline group before Gn administration, which reached statistical difference (P < 0.05). The mean length of Gn stimulation were (9.8 ± 1.7) days in low dose leuprorelin group, (10.5 ± 1.8) days in high dose of leuprorelin group and (11.1 ± 1.4) days in diphereline group, which reached statistical difference (P < 0.05). The mean dose of Gn was (24 ± 7) in low dose of leuprorelin group, which was significantly higher than (27 ± 9) in high dose of leuprorelin group and (28 ± 7) in diphereline group (P < 0.05). The level of LH was (2.7 ± 1.6) U/L in low dose of leuprorelin group and (2.2 ± 1.0) U/L in diphereline group before Gn administration, which reached statistical difference (P < 0.05). The cancel cycles were 5 in low dose of leuprorelin group, 4 in high dose of leuprorelin group and 7 in diphereline group. The number of ovum was (14 ± 7) low dose of leuprorelin group, (13 ± 6) in high dose of leuprorelin group, (14 ± 6) in diphereline group. The rates of fertilization was 66.26% (758/1144) in low dose of leuprorelin group, 67.01% (589/879) in high dose of leuprorelin group and 68.54% (1111/1621) in diphereline group, the rates of good-quality embryos was 64.22% (472/735) in low dose of leuprorelin group, 60.50% (340/562) in high dose of leuprorelin group and 59.59% (640/1074) in diphereline group, clinical pregnancy was 49% (38/78) in low dose of leuprorelin group, 42% (27/64) in high dose of leuprorelin group and 50% (55/110) in diphereline group, early miscarriage was 18% (7/38) in low dose of leuprorelin group, 15% (4/27) in high dose of leuprorelin group and 15% (8/55) in diphereline group, which did not show significant differences (P > 0.05). Both 1.25 mg and 1.88 mg leuprorelin acetate could obtain good down-regulation effect and clinical outcomes. 1.25 mg leuprorelin acetate could decrease patient's costs by reducing Gn dose and duration.

Dynamic measurements of serum inhibin B and estradiol: apredictive evaluation of ovarian response to gonadotrophin stimulation in the early stage of IVF treatment

We dynamically measured serum inhibin B and estradiol in the early stage of hormonal stimulation to predict the ovarian response in in vitro fertilization (IVF) treatment. A total of 57 patients (<40 years of age) who underwent the first cycle of long protocol IVF or introcytoplasmic sperm injection (ICSI) treatment were included. Serum inhibin B, estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured four times: (1) on Day 3 of the menstrual cycle (basal); (2) on the day before the first administration of gonadotrophin (Gn) (Day 0); (3) on Day 1 of Gn therapy; and (4) on Day 5 of Gn therapy. Comparisons of these measurements with ovarian responses and pregnancy outcomes were made and analyzed statistically. (1) On Day 1 and Day 5 of recombinant FSH (rFSH) stimulation, ovarian response, i.e., numbers of follicles, oocytes, fertilized oocytes, and embryos, had a positive correlation (r(s)=0.46~0.61, P=0.000) with raised inhibin B and estradiol concentrations, but a negative correlation (r(s)=-0.67~-0.38, P=0.000 or P<0.01) with total rFSH dose and total days of rFSH stimulation. (2) No significant variation (P>0.05) between the pregnant and non-pregnant groups on the basis of mean age or on all hormone concentrations at four times of the IVF cycle was observed. However, all the seven patients aged >35 years did not reach pregnancy. (1) Serum inhibin B and estradiol concentrations obtained shortly after Gn therapy may offer an accurate and early prediction of ovarian response; (2) Low levels of serum inhibin B and estradiol obtained shortly after Gn stimulation indicate the need for a longer period of Gn treatment and a higher daily dosage; (3) No obvious pregnancy difference among patients of age <35 years was found; however, IVF pregnancy outcome is significantly lower in women of age >35 years.

Oocyte quality and embryo quality of infertile women with polycystic ovarian syndrome

OBJECTIVE: To investigate the oocyte and embryo quality of infertile women with polycystic ovarian syndrome (PCOS), isolated polycystic ovaries morphology (PCO-only) or matched control group undergoing IVF-ET. DESIGN: A retrospective case-control study. MATERIALS AND METHODS: 486 IVF/ ICSI cycles were performed from January 2003 to January 2008. The diagnosis of PCOS was based on Rotterdam criteria. Three study groups were identified: PCOS group (202 cycles), PCO-only group (PCO-only morphology, 134 cycles) and control group (normal ovarian response and age-matched,150 cycles). Oocyte and embryo morphorlogy, including perivitelline space, polar body, granular cytoplasm, smooth endoplasmic reticulum incidence, vacuolization and abnormal zona pellucida, were recorded. Pregnancy outcome were analyzed. RESULTS: Compared with control group, lower maturity rate of oocytes, lower fertilization rate, and fewer number of high-grade embryos were attained in PCOS and PCO-only groups, although more oocytes were retrieved and lower total dose of gonadotropin were administrated (P<0.01). The percentage of transferred two high-quality embryo and total embryo score were lower in PCOS and PCO-only group compared to control group (P<0.05). There were no significant differences of the rate of abnormal perivitelline space, abnormal polar body, abnormal granular cytoplasm, smooth endoplasmic reticulum incidence, vacuolization and abnormal zona pellucida among the three groups in ICSI cycles (P>0.05). But total rate of MII oocyte morphology abnormality was significantly higher in PCOS and PCO-only group compared with control group (P<0.05). Clinical pregnancy were 51.0%, 53.0% and 46.0% in PCOS, PCO-only and control groups, respectively. No significant differences were noted in the implantation and pregnancy rates among the three groups. However the clinical miscarriage rate was significantly higher in women with PCOS group (15.4%) than that in the PCO-only morphology group (5.5%) and control group(5.8%)(P < 0.05). CONCLUSIONS: Infertile women with PCOS have shown to have similar characteristics to women with PCO-only in terms of ovarian response to Gn stimulation, oocyte and embryo quality and pregnancy rates. Oocyte morphology abnormality and embryo quality may be associated with early miscarriage rates in PCOS. It suggested that factors related to oocyte and embryo morphology present in PCOS patients may be instrumental in adverse reproductive outcomes in these women.

The outcome of different dose GnRH agonist suppression on in vitro fertilization-embryo transfer (IVF-ET) cycle outcome in patients with stage III/IV endometriosis

To evaluate the efficacy of different dose of GnRH agonist hormonal suppression on IVF-ET outcome in the patients with moderate or severe endometrosis. Retrospective study in tertiary university hospital encompassing the time period January 1, 2003∼December 30, 2006. Chinese women for IVF-ET with a primary diagnosis of stages III to IV endometriosis surgically confirmed and their first cycles in our center were included. Group I (61 patients) received standard COH employing mid-luteal phase GnRHa down regulation. Group II (35 patients) received monthly GnRHa 3.75 mg IM ×2 followed by ovarian hyperstimulation. Group III (44 patients) received monthly GnRH agonist 3.75 mg IM ×3 followed by ovarian hyperstimulation. All patients received ovarian stimulation with Gonadotrophin and hCG for triggering. Oocytes retrieval were scheduled 36 hours after hCG. Embryos were transferred at 4∼8 cell stage. Pregnancy rate (PR) were defined as sonographically visualized pregnancy sac. One-way analysis of variance (ANOVA) and Chi square analysis where appropriate. There were no significant differences among the groups with regards to age, duration of infertility, fertilization rate, embryos transferred. Women pretreatment with two or three months of GnRHa required significantly higher gonadotropin doses (ampoules:75IU) (group I: 42.76 ± 16.30, group II: 55.94 ± 23.38, group III: 63.88 ± 26.72, P<0.0001) and longer duration of Gn stimulation than women with standard long protocol (group I: 10.69 ± 1.68, group II: 12.59 ± 2.19, group III: 12.33 ± 2.26, P<0.0001). The number of oocytes was lower in group III than group I and II (group I: 10.22 ± 7.18, group II: 10.24 ± 6.89, group III: 7.07 ± 4.96, P=0.034). Pregnancy rate in group II was higher than group I and III, but that was not significant (group I: 28.6%, group II: 45.2%, group III: 35.1%, P>0.05). Implantation rate was also higher in group II than group I and III, but not significantly (group I: 14.9%, group II: 29.3%, group III: 17.57%, P>0.05). The administration of GnRH agonists to COH in women with moderate or severe endometriosis for a period of two to three months tend to increase the pregnancy rate. Two months of GnRHa (3.75 mg IM) prior to IVF appears to be a better option in Chinese women.

Clinical Analysis of Patients With Prolonged Duration of Gonadotrophin Administration in IVF/ICSI Treatment Cycle

In IVF/ICSI treatment cycles, some patients seem resistant to gonadotrophin stimulation and require prolonged stimulation time. They were served as a kind of poor responder and experience a higher cancellation. We report herein that pregnancies were got by prolonged use of gonadotrophin stimulation more than 16 days and characristics of these patients was analyzed compared to normal responder. Prospective study A total of 712 IVF/ICSI cycles, started GnRH agonist with a long protocol regimens, was performed between Jan.2003 to Jan.2005. Standard luteal-long GnRH agonist with rFSH or and HMG was applied to all patients. Day 3 embryo transfer was performed in these patients. The selection of criteria used to categorize the normal responder is that duration of gonadotrophin (Gn) stimulation is ≤15 days, total Gn ampoules used is ≤44 and tatoal oocytes retrieved is ≥4. The criteria for prolonged duration of gonadotrophin stimulation is that duration of stimulation is ≥16 days. Prolonged stimulation group (Group 1: n=63 transfer cycles) and normal response group ((Group 2: n=439 transfer cycles) were got and analyzed. Values were expressed as mean±SD and number(percent). There was no statistically difference of patient’s age, number of embryo transfer and miscarriage rate between two groups. There were more PCO/PCOS patients, longer duration of Gn stimulation (range 16-34 days), less oocytes, higher Gn dose, lower clinical pregnancy rate and lower OHSS rate in group 1 compared with group 2. But clinical pregnancy rate (44.4%) is pretty acceptable in group 1. Tabled 1 These results demonstrated that prolonged gonadotrophin stimulation more than 16 days is an alterative before cancellation of the IVF cycles for some poor responder during ovarian stimulation. Good clinical outcome can be got including pregnancy rate and lower OHSS rate by using prolonged gonadotrophin stimulation protocol in some poor responder compared with normal responder.