The effect of repeated controlled ovarian stimulation cycles on the gamete and embryo development

Zygote ◽  
2019 ◽  
Vol 27 (05) ◽  
pp. 347-349 ◽  
Author(s):  
L.T. Paul ◽  
O. Atilan ◽  
P. Tulay

SummaryThe aim of this study was to investigate if there is an adverse effect of multiple controlled ovarian stimulation (COS) on the maturity of oocytes (MI and MII), fertilization rate, embryo developmental qualities and clinical pregnancy rates in donation cycles. In total, 65 patients undergoing oocyte donation cycles multiple times were included in this study. Patients were grouped as group A that consisted of donors with ≤2 stimulation cycles while B consisted of donors with ≥3 stimulation cycles; and group C included donors who had ≤15 oocytes, while group D had donors with ≥16 oocytes. Numbers of oocytes obtained, MI and MII oocytes, fertilization, embryo quality and clinical pregnancy outcomes were compared. Significant statistical differences were observed in total number of oocytes obtained, maturity of oocytes (MI and MII), fertilization rate, embryo qualities and clinical pregnancy outcomes of donors in groups A–D. Donors with ≤2 ovarian stimulation cycles had lower numbers of immature oocytes than donors with three or more stimulation cycles. However, donors with ≥3 stimulation cycles had higher numbers of mature oocytes, zygotes, with better day 3 embryo qualities and higher clinical pregnancy rates than donors with ≤2 stimulation cycles. Repeated COS does not seem to have any adverse effect on ovarian response to higher dose of artificial gonadotropin, as quality of oocytes collected and their embryological developmental potential were not affected by the number of successive stimulation cycles. The effect of multiple COS on the health of the oocyte donor needs to be assessed for future purpose.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J A Moreno ◽  
P Masoli ◽  
C Sferrazza ◽  
H Leiva ◽  
O Espinosa ◽  
...  

Abstract Study question Is dydrogesterone (DYG) equivalent compared to cetrorelix with respect to clinical pregnancy rate, ongoing pregnancy rate and live birth rate in oocyte donation (OD) cycles? Summary answer DYG is comparable to cetrorelix in terms of clinical pregnancy, but higher rates of ongoing pregnancy and live birth were observed in the DYG group What is known already Progestin-primed ovarian stimulation (PPOS) is an ovarian stimulation regimen based on a freeze-all strategy using progestin as an alternative to GnRH analog for suppressing a premature LH surge. DYG is an oral progestin that has been studied in PPOS protocols. Published reports indicate that length of ovarian stimulation, dose of gonadotrophin needed and number of MII retrieved from PPOS cycles are comparable to short protocol of GnRH agonists during OD cycles. However, while some studies noted no differences in terms of live births, worse pregnancy rates have been reported in recipients of oocytes from PPOS cycles compared to GnRH antagonists. Study design, size, duration Prospective controlled study to assess the reproductive outcomes of OD recipients in which the donors were subjected to the DYG protocol (20mg/day) compared with those subjected to the short protocol with cetrorelix (0.25 mg/day) from Day 7 or since a leading follicle reached 14 mm. The OD cycles were triggered with triptoreline acetate and the trigger criterion was ≥3 follicles of diameter >18mm. Participants/materials, setting, methods 202 oocyte donors were included, 92 under DYG and 110 under cetrorelix. The study was performed in a private infertility center between January 2017 and December 2020. The main outcome included the rates of clinical pregnancy, ongoing pregnancy and live births. Secondary outcomes included the number of oocytes retrieved, number of MII, fertilization rate, length of stimulation and total gonadotropin dose. Differences were tested using a Student’s t-test or a Chi2 test, as appropriate. Main results and the role of chance Compared to antagonist cycles, cycles under DYG had fewer days of stimulation (9.9 ± 0.9 vs. 10.8 ± 1.1, p<.001) and a lower total gonadotropin dose (1654 ± 402.4 IU vs. 1844 ± 422 IU, p<.001). The number of MII retrieved was no different: 16.9 (SD 6.2) with DYG and 15.4 (SD 5.8) with cetrorelix (p = 0.072). Recipients and embryo transfer (ET) characteristics were also similar between groups. The mean number of MII assigned to each recipients was 6.7 (SD 1.8) in DYG and 6.6 (SD 1.7) in cetrorelix (P = 0.446). The fertilization rate was 66.2% in DYG versus 67.6% in cetrorelix (P = 0.68). Regarding the reproductive outcomes, the overall clinical pregnancy rate in DYG group (65/87: 74.7%) and cetrorelix group (66/104: 63.4%) (p = 0.118) was similar. Meanwhile, the DYG group compared to cetrorelix group had higher rates of ongoing pregnancy (63.2% vs 45.1%; p = 0.014) and live births (54,9% vs 37.8%; p = 0.040). Limitations, reasons for caution These results should be evaluated with caution. The limitations of this study include the limited number of participants enrolled and the limited data on pregnancy outcomes. A randomized controlled trial is necessary to provide more evidence on the efficacy of the DYG protocol. Wider implications of the findings: The efficacy of PPOS protocol compared to GnRH-antagonist protocol in terms of reproductive outcomes has been little studied. PPOS using DYG yields comparable clinical pregnancy rates compared to cetrorelix in OD cycles. The differences found regarding the rates of ongoing pregnancy and live births should be further investigated. Trial registration number Not applicable


2002 ◽  
Vol 78 ◽  
pp. S49 ◽  
Author(s):  
William H Catherino ◽  
Mark Leondires ◽  
Jeffrey McKeeby ◽  
David Cruess ◽  
James H Segars ◽  
...  

2019 ◽  
Author(s):  
Rong Li ◽  
Rui Yang ◽  
Yan Sheng ◽  
Fei Gong ◽  
Jianqiao Liu ◽  
...  

Abstract Background The prevalence of infertility among Chinese women of reproductive age was estimated to be 25.0%. Currently, assisted reproductive technology, such as in vitro fertilization (IVF), is considered the most effective treatment for infertility. Cetrorelix is a subcutaneously administered gonadotropin-releasing hormone antagonist approved for clinical use in IVF therapy. To improve IVF outcomes, there is a need to identify predictive markers of successful clinical pregnancy with gonadotropin-releasing hormone antagonists.Methods The retrospective FASSION study assessed clinical outcomes and factors associated with clinical pregnancy rates of Chinese patients undergoing fertility treatment with cetrorelix and IVF/intracytoplasmic sperm injection (ICSI) cycles. We analyzed medical records of infertile women aged ≤35 years, with baseline serum follicle-stimulating hormone level ≤10 mIU/mL, body mass index ≤30 kg/m2 and normal uterine cavity, who underwent IVF/ICSI cycles using cetrorelix at four centers in China. The primary objective was identifying factors associated with clinical pregnancy rates by validating a predictive model for clinical outcome evaluation. Secondary objectives were clinical outcomes and safety.Results In total, 2972 women were included. After adjusting for confounders, on the day of human chorionic gonadotropin triggering, an increased endometrial thickness was associated with a higher probability of pregnancy outcome (p=0.0001) and a higher progesterone level was associated with a lower probability of pregnancy outcome after fresh embryo transfer (ET) per initiated cycle (p=0.0256). Per ET cycle, the ongoing pregnancy and clinical pregnancy rates were 45.2% and 53.0%, respectively, with an implantation rate of 37.3% per ET. The early miscarriage and cycle cancellation rates were 13.4% and 5.7%, respectively. A total of 970 live births were reported. The live birth rate per initiated cycle was 32.6% and that per ET cycle was 45.2%. Fifty-one patients (1.7%) reported an ovarian hyperstimulation syndrome event, with severe events in 17 (0.6%) patients.Conclusions This prediction model may be useful for the preliminary screening of IVF patients and help improve clinical pregnancy outcomes.


2019 ◽  
Vol 70 (9) ◽  
pp. 3392-3398
Author(s):  
Dragos Nicolae Albu ◽  
Alice Ioana Albu ◽  
Gabriel Octavian Olaru ◽  
Romina Marina Sima ◽  
Adrian Neacsu ◽  
...  

Aim of the study was to analyse the relationship between Anti-M�llerian Hormone (AMH) serum level and in vitro fertilisation (IVF) with and without intra-cytoplasmic sperm injection (ICSI) outcome. We performed a retrospective study which included 1073 patients (mean age 34.68�4.28 years, mean body mass index 22.7�15.65 kg/m2) who performed IVF or IVF/ICSI between January 2013 and December 2016.We found that AMH serum level was age-independent positively related with oocytes (beta=0.329, p[0.0001) and zygotes number (beta=0.248, p[0.0001) and negatively correlated with fertilization rate (beta=-0.108, p=0.001). In multivariate regression, after adjustment for confounders, only oocytes number, but not AMH serum level, was associated with zygotes number (beta=0.814, p[0.0001) and fertilisation rate (beta=- 0.133, p=0.001). Patients with AMH in the range 1.1-5 ng/mL had significantly higher biochemical (65.3% versus 56.6%, p=0.009) and clinical pregnancy rates (57.7% versus 49.2%, p=0.014) in comparison with patients with AMH below 1.1 ng/mL and higher clinical pregnancy rates in comparison with patients with AMH above 7 ng/mL (57.7% versus 44%, p=0.011). Logistic regression analysis showed that AMH was positively associated with biochemical (OR 1.19, p=0.003) and clinical pregnancy (OR 1.16, p=0.009) independently of age and number of good embryos transferred in patients with AMH below 5 ng/mL. In turn, when only patients with normal ovarian reserve were analysed (AMH above 1.1 ng/mL), we found an age-independent negative association between AMH and clinical pregnancy (OR 0.93, p=0.014). AMH serum level is associated with both quantitative response (oocytes number) and qualitative parameters (pregnancy rate) during IVF/ICSI. We also found a bimodal relationship between AMH and pregnancy rates, which were positively associated in patients with AMH below 5 ng/mL, although higher AMH values seem to have a negative impact on pregnancy chances.


2020 ◽  
Vol 27 (1) ◽  
pp. 48-66 ◽  
Author(s):  
Baris Ata ◽  
Martina Capuzzo ◽  
Engin Turkgeldi ◽  
Sule Yildiz ◽  
Antonio La Marca

Abstract BACKGROUND Progestins are capable of suppressing endogenous LH secretion from the pituitary. Progestins can be used orally and are less expensive than GnRH analogues. However, early endometrial exposure to progestin precludes a fresh embryo transfer (ET), but the advent of vitrification and increasing number of oocyte cryopreservation cycles allow more opportunities for using progestins for pituitary suppression. OBJECTIVE AND RATIONALE This review summarizes: the mechanism of pituitary suppression by progestins; the effectiveness of progestins when compared with GnRH analogues and with each other; the effect of progestins on oocyte and embryo developmental potential and euploidy status; and the cost-effectiveness aspects of progestin primed stimulation. Future research priorities are also identified. SEARCH METHODS The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, the Web of Science and Scopus were screened with a combination of keywords related to ART, progesterone, GnRH analogue and ovarian stimulation, in various combinations. The search period was from the date of inception of each database until 1 April 2020. Only full text papers published in English were included. OUTCOMES Overall, the duration of stimulation, gonadotrophin consumption and oocyte yield were similar with progestins and GnRH analogues. However, sensitivity analyses suggested that progestins were associated with significantly lower gonadotrophin consumption than the long GnRH agonist protocol (mean difference (MD) = −648, 95% CI = −746 to −550 IU) and significantly higher gonadotrophin consumption than the short GnRH agonist protocol (MD = 433, 95% CI = 311 to 555 IU). Overall, live birth, ongoing and clinical pregnancy rates per ET were similar with progestins and GnRH analogues. However, when progestins were compared with GnRH agonists, sensitivity analyses including women with polycystic ovary syndrome (risk ratio (RR) = 1.27, 95% CI = 1.06 to 1.53) and short GnRH agonist protocols (RR = 1.14, 95% CI = 1.02 to 1.28) showed significantly higher clinical pregnancy rates with progestins. However, the quality of evidence is low. Studies comparing medroxyprogesterone acetate, dydrogesterone and micronized progesterone suggested similar ovarian response and pregnancy outcomes. The euploidy status of embryos from progestin primed cycles was similar to that of embryos from conventional stimulation cycles. Available information is reassuring regarding obstetric and neonatal outcomes with the use of progestins. Despite the lower cost of progestins than GnRH analogues, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase cost per live birth with progestins as compared to an ART cycle culminating in a fresh ET. WIDER IMPLICATIONS Progestins can present an effective option for women who do not contemplate a fresh ET, e.g. fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, double stimulation cycles.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Lubamba

Abstract Study question Are pregnancy rates after intra uterine insemination-donor sperm (IUI-D) in good prognosis patients with controlled ovarian stimulation (COS) different from those in natural cycles? Summary answer In good prognosis patients, IUI-D cycles with COS provided higher pregnancy outcomes compared to IUI-D in natural cycles. What is known already There is no consensus about the systematic use of COS for IUI-D in good prognosis patients, considering efficacy, safety, and efficiency. The objective of this study is to compare the clinical pregnancy rate in good prognosis patients undergoing an IUI-D cycle with COS versus natural cycle (NC). Study design, size, duration Retrospective cohort study of 5,369 first IUI-D performed between January 2012 and September 2019 in one fertility center. IUI-D with COS (n = 4,417) versus natural cycles (n = 952) were compared. Differences in pregnancy outcomes between study groups were evaluated using a Pearson’s Chi2 test. A p < 0.05 was considered statistically significant. Participants/materials, setting, methods Good prognosis patients were defined as women aged ≤38 years old, with a BMI ≤35 Kg/m2, and having regular menses. The indications for IUI-D were an absence of male partner or a sever partner male factor. COS consisted in a standard protocol of r-FSH or hMG-HP, in a dose between 25 IU to 75 IU, depending on the patient’s age and the acceptance of multiple pregnancy, to obtain between 1 to 2 follicles at ovulation. Main results and the role of chance Average age was slightly higher in COS patients (33.0±3.8 versus 31.6±4.1 years old in NC), as was BMI (23.7±3.6 in COS vs 23.08±4.1 in NC). Further, in the last follicular control, estradiol was higher (321±180 vs 244±108 pg/ml), LH was lower in (14 vs 28 UI/L), and the number of follicles > 16mm was higher (1.06±0.5 vs 0.96±0.4) in COS vs NC, respectively. Progesterone levels did not differ between groups. Stimulated cycles provided significantly better results for all pregnancy outcomes (p < 0.001): biochemical pregnancy rate was 27.8% in COS versus 23.0% in NC; clinical pregnancy rate was 20.5% versus 14.8%; ongoing pregnancy rate was 18.5% versus 13.3%; and live birth rate was 16.8% versus 12.3%. While the analysis was not adjusted for potential confounding factors, baseline characteristics between groups were very similar, so we could expect that the improved reproductive results were due to COS. Limitations, reasons for caution The main limitation of the study is its retrospective nature and the collection of data from one clinic. Differences found between study groups should be confirmed in a prospective controlled trial. Wider implications of the findings: In good prognosis patients undergoing their first IUI-D, controlled ovarian stimulation provides better reproductive outcomes; further analysis of cumulative pregnancy rate after 3 cycles would provide information for recommendations on the complete treatment cycle. Trial registration number non applicable


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
T A Raafat ◽  
H F Mohammad ◽  
E I Hassan

Abstract Background Infertility is an illness clinically defined as failure to achieve a clinical conception after 12 months of regular and unprotected normal sexual intercourse. It affects around 8 -12% of child bearing-aged couples globally. Premature progesterone elevation is considered for a long time a cornerstone factor to endometrial implantation failure. Although the extensive usage of GnRH analogues for down-regulation of pituitary, rise in progesterone serum levels, still occur at various levels on the day of administration of hCG for ultimate oocyte maturity in fresh IVF management cycles. Aim to investigate and evaluate the correlation between serum progesterone level on the day of HCG administration and the clinical pregnancy rate as a primary outcome, quality of embryo, quality of oocyte, fertilization rate and chemical pregnancy assessed by B-HCG level 2 weeks after embryo transfer as secondary outcomes. Methodology This prospective non interventional study was conducted at Assisted Reproduction Unit, Ain Shams University Maternity Hospital, Cairo, Egypt, starting from December 2015 till March 2017. The study included 240 women scheduled for ICSI presented with primary or secondary infertility, the causes of infertility in this study were male factor, tubal factor and unexplained infertility. Results the current research study displayed that there was unfavorable statistical correlation between serum progesterone elevation at the day of HCG trigger and the clinical pregnancy rates which was 34.2%, the cut off value of serum progesterone was 1.09 ng/ml; above this value the serum pregnancy rates were negatively influenced. Additionally premature rise of serum progesterone levels reduced the embryonic quality, oocyte quality and fertilization rate. Conclusion serum progesterone level equal to or above 1.09 ng/ml at the day of HCG trigger unfavorably influences on the clinical pregnancy rates in ICSI cycles. Recommendations All embryos should be cryopreserved when serum progesterone on the day of HCG trigger equals to or above 1.09 ng/ml during ICSI cycle to be transferred in subsequent cycle to avoid implantation failure.


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