First Day Of Ovarian Stimulation Research Articles

Comparing blastocyst euploid rates between the progestin-primed and gonadotrophin-releasing hormone antagonist protocols in aneuploidy genetic testing: a randomised trial protocol

IntroductionProgestin can inhibit the pituitary luteinising hormone (LH) surge during ovarian stimulation for in vitro fertilisation (IVF) and studies show progestin-primed ovarian stimulation (PPOS) is effective in blocking the LH...

Effects of time of recombinant luteinized hormone supplementation on pregnancy outcomes of women with advanced reproductive age during follicular-phase long protocol

Objective: To investigate the effects of supplementation of recombinant luteinized hormone (rLH) and its timing on pregnancy outcomes of patients at 35 years or older with follicular-phase long protocol. Methods: Clinical data of women undergoing in vitro fertilization or intracytoplasmic sperm injection with follicular-phase long protocol was collected and retrospectively analyzed in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2019. There were 558 patients at 35 years or older included in this study, and they were divided into three groups: group A was patients with only recombinant follicle stimulating hormone (rFSH) stimulation (127 cycles), group B was patients with rFSH plus rLH supplementation in the mid-follicular phase (141 cycles), and patients in group C received combined rFSH and rLH from the first day of ovarian stimulation (290 cycles). The basic characteristics of patients of each group were observed and the effects of ovarian simulation and pregnancy outcomes were compared among the three groups. Logistic regression model was performed to explore the association between different groups and pregnancy outcomes. Results: The basic characteristics such as age, duration of infertility, body mass index (BMI) and serum basic follicle stimulating hormone (FSH) were comparable among the three groups (all P>0.05). Anti-Müllerian hormone (AMH), antral follicles count (AFC) and basic luteinized hormone (LH) were significantly lower in group C compared to group A and group B (all P<0.05). There were statistically significant differences in initiation dosage, total dosage and duration of gonadotropin (Gn) among the three groups (all P<0.01), the initiation dosage, total dosage and duration of Gn were higher in group C than the other two groups. The number of oocytes retrieved and available embryos were significantly lower in group B and group C than group A (all P<0.001). In fresh embryo transfer cycles, significantly higher implantation rate (45.3%, 117/258) and clinical pregnancy rate (52.6%, 111/211) were found for group C when compared with group A and group B (P=0.036, P=0.006). The live birth rate in fresh embryo transfer cycles was comparable among the three groups (P=0.098). The implantation rate, clinical pregnancy rate and live birth rate in the subsequent frozen-thawed embryo transfer cycles did not differ significantly among the three groups (all P>0.05). There were no significantly differences in the cumulative pregnancy rate and the cumulative live birth rate among the three groups (all P>0.05). After adjusted for age, BMI, AMH, AFC, basic FSH and LH, total Gn dosage, endometrial thickness at transfer, number of oocytes retrieved, number of embryos transferred and stage of embryo transferred, in fresh embryo transfer cycles, the clinical pregnancy rate (adjusted OR=2.793, 95%CI: 1.512-5.162, P<0.001) and live birth rate (adjusted OR=2.324, 95%CI: 1.241-4.351, P=0.008) were higher in group C, while clinical pregnancy rate and live birth rate were similar between group B and group A in fresh embryo transfer cycles (all P>0.05); there was no significant difference in cumulative live birth rate among the three groups (P>0.05). Conclusions: The supplementation of rLH from the first day of ovarian stimulation improves the pregnancy outcomes of patients at 35 years or older in fresh embryo transfer cycles during follicular-phase long protocol. However, the supplementation of rLH has no benefit on cumulative live birth rate.

The unique opportunities and obstacles when integrating personal air pollution monitoring into studies of human fertility

BACKGROUND AND AIM: Exposure to air pollution has been associated with increased risk of infertility and pregnancy loss; however, the majority of research to date has relied on indirect measurements of air pollution which may have significant limitations due to the temporal and spatial variability of outdoor air pollution and the limited time that people spend outdoors. Directly measuring personal exposure to air pollution is a growing topic of interest, particularly in reproductive epidemiology, given the relatively short time windows of exposure susceptibility. METHODS: The Air Pollution, In Vitro Fertilization (IVF), and Reproductive Outcomes (AIR) Study recruited women undergoing a fresh, autogulous IVF cycle at the Massachusetts General Hospital Fertility Center. On the first day of ovarian stimulation, women were instructed to wear a personal particulate matter (PM) air pollution monitor (AirBeam2©), which measures three size fractions of particulate matter (PM1, PM2.5, and PM10), temperature, humidity, and GPS location, and complete a time-activity diary for the following 72-hour period. RESULTS:Between September 2018 and November 2019, 14 (out of 31 eligible) women enrolled in the AIR Study. The majority (71%) of women who did not enroll began ovarian stimulation on the weekend, when study staff were not regularly in clinic. 10 women successfully collected air pollution data for a median (minimum, maximum) of 41.5 (8.4, 64.5) hours during ovarian stimulation. The median (interquartile range) exposure to PM1, PM2.5, and PM10 was 0.7 (4.1), 2.1 (5.5), 3.2 (8.3) μg/m3, respectively. During this 72-hour window, women spent the majority of their time (72%) inside at home. Among the 4 women who were unsuccessful with the air monitors, limited battery life and frequent connection issues were cited as the main issues. CONCLUSIONS:Personal air pollution monitors can be utilized to characterize short-term exposure and, when applied appropriately, may greatly enhance our understanding of how air pollution affects human reproduction. KEYWORDS: air pollution, particulate matter, reproductive outcomes, short-term exposure, exposure assessment

Trajectories and predictors of anxiety and depression amongst infertile women during their first IVF/ICSI treatment cycle

PurposeThis study aimed to identify anxiety and depression trajectories of infertile women during first IVF treatment cycle and to examine whether the identified trajectories were associated with baseline psychological predictors, namely fertility-related stress, resilience, and illness perception. MethodsA longitudinal prospective study was conducted to assess anxiety and depression using the Chinese version of Self-Rating Anxiety Scale (SAS) and Self-Rating depression Scale (SDS) at four different time points: the day of first IVF/ICSI appointment (baseline/T1), the first day of ovarian stimulation (T2), the one day before oocyte retrieval (T3), and the day of fresh embryo transfer (T4). Final analysis was done on data obtained from 202 infertile women. Latent class growth mixed modeling was carried out to identify anxiety and depression trajectories. Multinomial logistic regressions were conducted to investigate predictors of trajectory membership. ResultsThree different adjustment trajectories were identified amongst infertile women during their first IVF/ICSI treatment cycle. A total of 40.1 and 37.6% of women showed normal levels of anxiety and depression (resilient trajectories), respectively, 45.0 and 43.1% of women had recovery trajectories, and 14.9 and 19.3% of women had chronic anxiety and depression trajectories. Non-resilient trajectories were associated with relatively shorter duration of infertility, higher fertility-related stress, and lower resilience. ConclusionThe results imply that it is possible to identify women in chronic or recovery trajectories on the day of first IVF/ICSI appointment, so that tailored prevention strategies integrated components that attenuate stress appraisal and strengthen resilience should be implemented to target those individuals.

THE USE OF DYDROGESTERONE TO PREVENT LH PEAK IN RANDOM-START OVARIAN STIMULATION FOR FERTILITY PRESERVATION

Compare the efficacy of oral dydrogesterone to prevent LH peak during ovarian stimulation versus usual antagonist protocol in fertility preservation cases with oocyte vitrification. Randomized prospective study from August 2019 to March 2020 at the Gynecology, Obstetric and Reproductive Medicine department of the Aziza Othmana University Hospital. Inclusion criteria: All patients underwent controlled ovarian stimulation for fertility preservation via oocyte vitrification. Exclusion criteria: Patients with hormone-dependent diseases (breast cancer, systemic lupus). Random-start ovarian stimulation was conducted with 300 IU of recombinant FSH for all patients. Patients were randomized into 2 groups on the day of the onset of ovarian stimulation: Group 1: prevention of LH peak using Dydrogesterone orally: 10 mg three times a day; beginning the first day of ovarian stimulation. Group 2: Prevention of LH peak by subcutaneous injection of Cetrotelix 0.25 mg per day from the first day of ovarian stimulation. Ovulation was triggered with 0.2 mg triptoreline. Oocyte pickup took place 37 hours later, either vaginally or per urethral transvesical route (for virgin patients). χ2 test was used to compare qualitative variables. Student’s t-test was used to compare quantitative variables. P-value < 0.05 was considered as statistically significant. Forty-seven patients were included in our study: 22 in Group 1 and 25 in Group 2. There was no significant difference regarding the clinical characteristics of the 2 groups (Group 1 vs Group 2) in terms of age (23.14 ± 5.07 vs 23.8 ± 5.7 , p: 0.7), BMI (21.63 ± 3.6 vs 22.48 ± 4.03 , p: 0.5), AMH levels (2.04 ± 1.24 vs 3.3 ± 1.93, p: 0.06), the duration of ovarian stimulation ( 9.14 ± 1.55 vs 9.33 ± 1.79 , p: 0.5), the number of follicles with a diameter > 15 mm on the day of triggering ( 7.62 ± 4.1 vs 7.5 ± 3.3, p: 0.6) and plasma oestrogen levels on the day of triggering ovulation (2587 ± 1601 vs 2083 ± 1163, p: 0.1) Moreover, pickup results were similar (goupe 1 vs group 2) for the number of CCOS( 12.71 ± 7.7 vs 12.29 ± 7.6 , p: 0.3) and the number of mature oocytes ( 9.85 ± 5.9 vs 9 ± 6.7 , p: 0.9). It should be noted that LH monitoring was performed in all patients and the difference was not significant either. Prevention of premature LH peak during COS is possible using dydrogesterone in Random-start protocols for fertility preservation, excluding cases of hormone-dependant diseases.

Randomized, Controlled Pilot Study of Low-Dose Human Chorionic Gonadotropin Administration Beginning From the Early Follicular Phase for Women With Polycystic Ovarian Syndrome Undergoing Ovarian Stimulation Using the Progesterone Protocol.

Purpose: To illustrate whether low-dose human chorionic gonadotropin (hCG) administration during the early follicular phase could reduce the number of large preovulatory follicles in women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation using the progesterone protocol.Methods: We performed a randomized, controlled pilot trial at a university-affiliated tertiary hospital. A total of 40 infertile women undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment with the freeze-all strategy were included. Human menopausal gonadotropin (hMG) and progesterone soft capsule 100 mg/d were added simultaneously beginning from menstrual cycle day 3 for all participants. Low-dose hCG (200 IU) was injected every 3 days in the study group from the first day of ovarian stimulation until trigger. The primary outcome was the number of large preovulatory follicles. Secondary outcomes included the incidence of ovarian hyperstimulation syndrome (OHSS); the number of oocytes retrieved, mature oocytes, and good-quality embryos; and clinical results after frozen-thawed embryo transfer (FET) cycles.Results: The study group had slightly more large preovulatory follicles than the control group (17.75 ± 10 vs. 13.2 ± 5.34; P > 0.05). None of the participants experienced severe OHSS. There were no statistically significant differences in the number of oocytes retrieved (15.9 ± 8.46 vs. 15.75 ± 6.96), mature oocytes (13.55 ± 6.56 vs. 13.4 ± 6.34), and good-quality embryos (5.5 ± 3.41 vs. 4.9 ± 2.99) between the two groups (P > 0.05). Clinical pregnancy rates (65.52 vs. 41.94%; P = 0.067) and live birth rates (48.28 vs. 35.48%; P = 0.315) per transfer following FET of the study group were higher than those of the control group, but without statistical significance.Conclusions: Administration of low-dose hCG from the early follicular phase for PCOS patients undergoing ovarian stimulation with progesterone protocol may lead to slightly more early preovulatory follicles and marginally, but not significantly, higher clinical pregnancy rates. A continuous trial should be performed to explore the effects of supplementation with different doses of hCG from the start of ovarian stimulation in PCOS patients using the progesterone protocol.Clinical Trial Registration: Chictr.org.cn, identifier: ChiCTR-IOR-15007165

The effect of intra-ovarian androgen priming on ovarian reserve parameters in Bologna poor responders

What are the effects of long-term androgen priming in Bologna criteria poor ovarian reserve (POR) patients undergoing IVF? This open-label pilot study was conducted at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. It included consecutive patients aged 18-41 years who fulfilled Bologna criteria for POR undergoing intra-ovarian androgen priming and ultra-long down-regulation with a gonadotrophin-releasing hormone agonist (GnRHa), followed by stimulation with gonadotrophins and GnRH antagonist co-treatment for IVF (n = 30). Priming consisted of low-dose recombinant human chorionic gonadotrophin (rHCG) 260 IU every second day plus letrozole 2.5 mg/day, both for 8 weeks; priming stopped on the first day of ovarian stimulation. The primary endpoint was serum anti-Müllerian hormone (AMH) concentration 8 weeks after priming. Secondary endpoints included antral follicle count (AFC) (2-10 mm), serum human chorionic gonadotrophin (HCG), testosterone and progesterone levels. Circulating testosterone, progesterone, oestradiol and HCG levels remained unchanged during androgen priming; the mean AMH level decreased steadily from 0.49 ng/ml (baseline) to 0.33 ng/ml (8 weeks). AFC was 4-5 throughout the study. A mean of 1.1 ± 0.9 good transferable embryos were obtained; embryo transfer was performed in 15 patients; no ongoing pregnancies were obtained. Long-term intra-ovarian androgen priming in the current set-up had no significant effect on hormone levels, AFC and recruitable follicles after ovarian stimulation in Bologna POR patients undergoing IVF. Further studies are needed to explore other androgen priming protocols and the clinical value of priming regimens in IVF.

Comparison of ultrasound-guided endometrial polypectomy carried out on the oocyte retrieval day and the first day of ovarian stimulation in IVF–ICSI cycles

In this retrospective cohort study, the effect of endometrial polypectomy carried out on the day of oocyte retrieval and on the first day of ovarian stimulation in patients with a large (≥10 mm) endometrial polyp undergoing IVF and intractyoplasmic sperm injection (ICSI) was investigated and compared. A total of 74 eligible IVF–ICSI cycles in 74 women who underwent endometrial polypectomy on either the day of oocyte pick-up (late polypectomy group, 39 cycles) or the first day of ovarian stimulation (early polypectomy group, 35 cycles) between January 2007 and July 2012 were included in this study. Patient characteristics between early and late polypectomy groups were similar. Total dose and days of recombinant human FSH administered, numbers of retrieved oocytes, mature oocytes, fertilized oocytes, grade 1 or 2 embryos and embryos transferred between the two groups were also similar, as was clinical pregnancy rate per cycle, embryo implantation rate and spontaneous abortion rate between the two groups. Therefore, endometrial polypectomy on the day of oocyte retrieval could be a more patient-friendly option for patients with a large endometrial polyp undergoing IVF–ICSI.

Highly purified hMG versus recombinant FSH plus recombinant LH in intrauterine insemination cycles in women ≥35 years: a RCT.

Is the treatment with recombinant FSH (rFSH) plus recombinant LH (rLH) more effective than highly purified (HP)-hMG in terms of ongoing pregnancy rate (PR) in women ≥35 years of age undergoing intrauterine insemination (IUI) cycles? The ongoing PR was not significantly different in women treated with rFSH plus rLH or with HP-hMG. Although previous studies have shown beneficial effects of the addition of LH activity to FSH, in terms of PR in patients aged over 34 years having ovulation induction, no studies have compared two different gonadotrophin preparations containing LH activity in women ≥35 years of age in IUI cycles. A single-centre RCT was performed between May 2012 and September 2013 with 579 women ≥35 years of age undergoing IUI cycles. The patients were randomly assigned to one of the two groups, rFSH in combination with rLH group or HP-hMG (Meropur) group, by giving them a code number from a computer generated randomization list, in order of enrolment. The randomization visit took place on the first day of ovarian stimulation. Five hundred and seventy-nine patients with unexplained infertility or mild male factor undergoing IUI cycles were recruited in a university hospital setting. All women were enrolled in this study only for one cycle of treatment. Five hundred and seventy-nine cycles were included in the final analysis. Two hundred and ninety patients were treated with rFSH in combination with rLH and 289 patients were treated with HP-hMG. The ovarian stimulation cycle started on the third day of the menstrual cycle and the starting gonadotrophin doses used were 150 IU/day of rFSH plus 150 IU/day of rLH or 150 IU/day of HP-hMG. The drug dose was adjusted according to the individual follicular response. A single IUI per cycle was performed 34-36 h after hCG injection. The main outcome measures were ongoing PR and number of interrupted cycles for high risk of ovarian hyperstimulation syndrome (OHSS). Ongoing pregnancy rates were 48/290 (17.3%) in the recombinant group versus 35/289 (12.2%) in the HP-hMG group [(odds ratio (OR) 1.50, 95% CI 0.94-2.41, P = 0.09]. The number of interrupted cycles for high risk of OHSS was 13/290 (4.5%) in the rFSH plus rLH group and 2/289 (0.7%) in the HP-hMG group (OR 6.73, 95% CI 1.51-30.12, P = 0.013). One of the limitations of this study was the early closure and the ongoing PR could be overestimated. Both patient and gynaecologist were informed of the assigned treatment. Our results demonstrated the lack of differences in terms of ongoing PR between recombinant product and HP-hMG, in women ≥35 years undergoing controlled ovarian stimulation for IUI cycles. HP-hMG was safer than recombinant gonadotrophin concerning the risk of OHSS. None. NCT01604044.

Does combined prednisolone and low molecular weight heparin have a role in unexplained implantation failure?

To study the effect of combined oral prednisolone and LMW heparin in ICSI in women with previously unexplained, failed implantation. A prospective quasi-randomized, controlled trial was conducted at a university teaching hospital and a private practice setting. A total of 334 cycles (women with previously unexplained, failed one or two ICSI attempts) were assigned randomly to receive standard treatment or combined prednisolone (20 mg/day), starting on the first day of ovarian stimulation and LMW heparin 1 mg/kg/day starting 1 day after oocyte retrieval in addition to standard treatment. The mean age, number of previously failed IVF attempts, and basal FSH levels were comparable between both groups. The pregnancy and the implantation rates were significantly different between the study and control groups. A combination of oral prednisolone and low molecular weight heparin may have a significant effect on pregnancy and implantation rates in prior unexplained, failed implantation.

The relationship between the change in serum high sensitivity C-reactive protein levels and IVF success

The aim of this study was to assess whether the extent of the change in high sensitivity C-reactive protein (hs-CRP) levels is related with in vitro fertilization (IVF) success. A total of 69 IVF cycles using long luteal GnRH agonist protocol at the IVF unit, were prospectively studied. The serum levels of hs-CRP were measured on the day of initiation of gonadotrophin stimulation and 7 days after embryo transfer. CRP ratio was defined as the levels of CRP on day 7 of transfer/day of initiation of ovarian stimulation. Clinical pregnancy rates were examined. The mean concentrations of hs-CRP were not significantly different on the first day of ovarian stimulation and on day 7 after embryo transfer among pregnant and non-pregnant women. There was a significant rise in hs-CRP levels at 7th day after embryo transfer as compared with the first day of gonadotrophin treatment in both groups (10.58 ± 11.35 versus 3.61 ± 2.86 mg/L for pregnant women and 9.14 ± 11.36 versus 3.24 ± 2.68 mg/L for non-pregnant women, p = 0.001). In addition, the mean CRP ratio was not different between the pregnant and non-pregnant groups. Our data show that serum hs-CRP levels increase during IVF treatment, but the extent of the rise in CRP levels is not a predictive marker of IVF success.

The psychological impact of mild ovarian stimulation combined with single embryo transfer compared with conventional IVF

The objective of this study was to assess the psychological implications of mild ovarian stimulation combined with single embryo transfer (SET) during a first IVF cycle. We conducted a randomized controlled two-centre trial. Three hundred and ninety-one couples were randomized to undergo either mild ovarian stimulation with GnRH antagonist co-treatment and SET (n=199) or conventional GnRH agonist long protocol ovarian stimulation with double embryo transfer (DET) (n=192). Women completed the Hospital Anxiety and Depression Scale, the Hopkins Symptom Checklist and the Subjective Sleep Quality Scale at baseline, on the first day of ovarian stimulation and following embryo transfer. Affect was assessed daily with the Daily Record Keeping Chart from the first day of ovarian stimulation until the day treatment outcome became known. The conventional IVF group experienced elevated levels of physical and depressive symptoms during pituitary downregulation. At oocyte retrieval, this group experienced more positive affect and less negative affect than the mild IVF group. In the conventional IVF group, cycle cancellation was associated with less positive and more negative affect. During the first IVF treatment cycle, mild ovarian stimulation and SET does not lead to more psychological complaints than conventional IVF.

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.

Serum leptin concentrations in patients with severe ovarian hyperstimulation syndrome during in vitro fertilization–embryo transfer treatment

To investigate the changes in serum leptin concentration in the conception cycle of severe ovarian hyperstimulation syndrome (OHSS). Prospective longitudinal study of 66 IVF-ET cycles between May 2000 and June 2002. Infertility outpatient clinic at a Japanese medical school. Infertile patients undergoing IVF-ET cycles at the infertility outpatient clinic were divided into three groups consisting of group 1 (conception-cycle patients with severe OHSS, n = 9), and group 2 (conception cycle, non-OHSS, n = 28), and group 3 (nonconception cycle, non-OHSS, n = 29). Blood samples were collected at five different periods. Period I, on the first day of ovarian stimulation with FSH; period II, at hCG administration before oocyte retrieval; period III, 7 days after oocyte retrieval; period IV, 14 days after oocyte retrieval; and period V, 21 days after oocyte retrieval. Serum leptin concentration. The serum leptin concentration was low in the OHSS group compared with that of the non-OHSS groups in all serum samples, with significant levels at periods III (vs. groups 2 and 3; P<.05) and IV (vs. group 3; P<.01). A twofold increase of leptin concentration from period I to period II (P<.05) was observed in all groups. The change pattern in serum leptin concentration might provide a great contribution to the pathophysiology development of OHSS patients during assisted reproductive treatment.

Serum leptin concentration during in vitro fertilization treatment with controlled ovarian hyperstimulation: Serum leptin concentration decreases in the early luteal phase in pregnancy

Purpose: To investigate the change pattern of leptin during in vitro fertilization and embryo transfer (IVF‐ET) treatment with controlled ovarian hyperstimulation (COH) and at the stages of very early pregnancy.Methods: The serum leptin concentration was investigated in 65 patients treated with assisted reproductive technology (ART) in five different periods (ART‐1: on the first day of ovarian stimulation with follicle‐stimulating hormone; ART‐2: at human chorionic gonadotropin administration before oocyte retrieval; ART‐3: 7 days after oocyte retrieval; ART‐4: 14 days after oocyte retrieval and ART‐5: 21 days after oocyte retrieval).Results: The leptin concentration showed significant lower values in the pregnancy group than the non‐pregnancy group at ART‐3 and ART‐4 (P &lt; 0.05). In the pregnancy group, leptin concentration increased from ART‐1 (13.5 ± 8.2 ng/mL) to ART‐2 (23.0 ± 15.1 ng/mL) (P &lt; 0.001). The values significantly decrease at 7 days after oocyte retrieval, from ART‐2 to ART‐3 (18.1 ± 12.0 ng/mL) (P &lt; 0.01), and then showed no remarkable change until 21 days after oocyte retrieval. In the non‐pregnancy groups, leptin concentration increased from ART‐1 (17.3 ± 11.5 ng/mL) to ART‐2 (25.7 ± 12.1 ng/mL) (P &lt; 0.0001). There was no remarkable change in leptin concentration until 14 days after oocyte retrieval, followed by a significant decrease in leptin concentration at ART‐4 (21.9 ± 11.9 ng/mL) to ART‐5 (18.1 ± 11.8 ng/mL) (P &lt; 0.05).Conclusion: The serum leptin concentration increases during COH in the pregnancy and non‐pregnacy groups. In the pregnancy group, leptin concentration showed a fall of leptin values at early luteal phase. These findings might be useful to elucidate the role of leptin in the IVF‐ET patients. (Reprod Med Biol 2003; 2: 177–182)

Advancing age is associated with increased AUC (area under the curve) for E2 (estradiol) production per mature follicle and decreased AUC per FSH stimulation irrespective to the protocol of ovarian stimulation

Objective: To study the effect of age on the pattern of estrogen production per mature ovarian follicle and in response to FSH stimulation during different ovarian stimulation protocols Design: Retrospective. Materials and Methods: Patients undergoing ovarian stimulation in conjunction with intrauterine insemination or for IVF-ET (in vitro fertilization and embryo transfer) have been included from two tertiary referral academic infertility centers in the period from January 2000 and July 2002. Patients were divided into two groups, first group included patients who underwent COH (controlled ovarian hyperstimulation) for IVF-ET (226 patients had 254 cycles). Both standard and microdose flare protocol were applied for COH. The second group included 357 patients who received different ovarian stimulation protocols in conjunction with IUI (intrauterine insemination) in 493 cycles. Clomiphene citrate was used alone in 176 cycles and in conjunction with FSH in 28 cycles, FSH injection alone in 87 cycles, letrozole (an aromatase inhibitor) was used alone in 84 cycles and in conjunction with FSH in 118 cycles). The AUC for E2 production was calculated from available daily E2 levels along the follicular phase starting on the first day of ovarian stimulation until the day of hCG administration (or endogenous LH surge in IUI cycles). AUC for E2 production per FSH unit administered (AUC/FSH) as well as the AUC for E2 produced per mature follicle (AUC/follicle) were calculated. Patients were sub-grouped according to the age in ascending matter. Each patient group was analyzed separately and after subdividing them according to the protocol of ovarian stimulation. Results: Group 1 (IVF) patients had a positive correlation between AUC/follicle and advancing age (P<0.05) and a negative correlation between AUC/FSH and advancing age (P<0.05). This was true when all patients were analyzed together and after subgrouping according to the stimulation protocol (long standard and microdsoe flare up protocol). The same findings were found in the second patient group when all patients were analyzed together and when subdivided into different ovarian stimulation protocol. Pregnancy rates negatively correlated well with advancing age as expected and was also negatively correlating with increasing AUC/follicle and decreasing AUC/FSH. The effect of age on AUC/follicle, AUC/FSH and Pregnancy Rate in IVF-ET cycles Tabled 1 View Large Image Figure ViewerDownload (PPT) Conclusions: High AUC/follicle and low AUC/FSH seem to be features of advancing age irrespective of type of ovarian stimulation. Both parameters also might serve as predictors for poor treatment outcome.

Pregnancy outcome and embryo quality depends on the serum progesterone levels on the first day of ovarian stimulation following in vitro fertilization

Objective: Previous studies suggested that initial serum levels of FSH and estradiol could be used to evaluate the potential of pregnancy outcome in IVF treatments. Higher levels of these hormones during natural cycle decrease the chance of pregnancy. In this study we evaluated the effect of progesterone (P4) values in serum on the first day of ovarian stimulation and if it could be used as an indicator for the initiation of ovarian stimulation and pregnancy outcome.

Effect of GnRH antagonist on vascular endothelial growth factor (VEGF) during ovarian stimulation cycle

Objective: VEGF is produced and released by granulosa-theca and endotelial cells. This factor is related to increase the vascular permeability and has also been related to ovarian response to ovarian stimulation(COH). The purpose of the present study was to compare the concentration of VEGF in the serum and follicular fluid from women undergoing controlled ovarian hyperstimulation treated with GnRH antagonist or agonist. Design: Prospective study. Materials/Methods: Twenty women with primary infertility undergoing IVF were included. Patients were randomized to two different COH protocols: (1): long mid luteal suppression with GnRH agonist, Triptorelin (Decapeptyl®0.1, Ipsen-Pharma) or (2) multiple doses of GnRH antagonist (Cetrotide® 0.25; Serono) with recombinant FSH (Gonal F®, Serono). In both groups ovarian stimulation was started on day 3 with 225 UI for 4 days, then individual dosage was adjusted according the follicular growth. Antagonist was started on day 6 until the day HCG administration. Blood samples were obtained in the first day of ovarian stimulation and daily after day 5 up to HCG administration. The day of ovum pick up, follicular fluid (FF) of 5 mature follicles (>16 mm diameter) was polled and also blood was withdrawn for analysis. VEGF was determined in serum and FF by ELISA (Quantikine®R&DSystens). Results: No significant differences were found between both groups in age (25.5 ± 6.1 vs 27.0 ± 4.0), length of stimulation days (7.8 ± 1.4 vs 9.1 ± 1.7), total FSH dose (1339 ± 226 vs 1596 ± 279), number of oocytes obtained (12 ± 6.7 vs 17.2 ± 5.7), number of metaphase II oocytes (10.2 ± 5.7 vs 15.4 ± 4.8) and fertilization rate (78.3% vs 81.4%). Conclusions: VEGF serum levels are stimulated by gonadotropins and down-regulated by both, agonists and antagonists of GnRH. However, FF VEGF levels are higher in antagonist cycles, suggesting that the process of angiogenesis may be less affected under this regimen of ovarian stimulation. Table TableVEGF serum and follicular fluid levels (pg/ml)Day 2–3Day 5Day 6Day 7Day HCGVEGF Follicular Fluid (pg/ml)Antagonist0,36 ± 0,20,57 ± 0,1†p < 0,050,51 ± 0,2†p < 0,050,37 ± 0,010,40 ± 0,190,46 ± 0,25Agonist0,28 ± 0,10,33 ± 0,1†p < 0,050,25 ± 0,1†p < 0,050,23 ± 0,060,30 ± 0,070,37 ± 0,17† p < 0,05 Open table in a new tab

Quantitative assessment of subendometrial blood flow by three-dimensional-ultrasound is an important predictive factor of implantation in an in-vitro fertilization programme.

This study was designed to investigate the role of three-dimensional (3D) power Doppler sonography of the (sub-) endometrial area on the first day of ovarian stimulation in predicting the outcome of an in-vitro fertilization (IVF) programme. Among the 75 cycles analysed, the overall pregnancy rate was 20% (15/75) per cycle and 23.8% (15/63) per embryo transfer. Intra-observer variability of the colour histogram was checked in 14 patients with the results demonstrating a high level of agreement. Neither endometrial measurements nor uterine blood flow were correlated with the pregnancy rate. In contrast, all 3D indices were significantly lower in conception compared with non-conception cycles (P < 0.05). Logistic regression analysis found the subendometrial flow index to be the strongest predictive factor of IVF success among the tested sonographic parameters (P = 0.04). In conclusion, quantitative assessment of spiral artery blood flow may be of predictive value for implantation in IVF cycles even before ovarian stimulation therapy is started.