scholarly journals Gonadotrophins or clomiphene citrate in women with normogonadotropic anovulation and CC failure: does the endometrium matter?

2020 ◽  
Vol 35 (6) ◽  
pp. 1319-1324
Author(s):  
E M Bordewijk ◽  
N S Weiss ◽  
M J Nahuis ◽  
J Kwee ◽  
A F Lambeek ◽  
...  
Keyword(s):  
Live Birth ◽  
Treatment Effect ◽  
Endometrial Thickness ◽  
Intrauterine Insemination ◽  
Controlled Trial ◽  
Clomiphene Citrate ◽  
Live Birth Rate ◽  
Ovulatory Cycle ◽  
Birth Rates ◽  
Live Birth Rates

Abstract STUDY QUESTION Is endometrial thickness (EMT) a biomarker to select between women who should switch to gonadotropins and those who could continue clomiphene citrate (CC) after six failed ovulatory cycles? SUMMARY ANSWER Using a cut-off of 7 mm for EMT, we can distinguish between women who are better off switching to gonadotropins and those who could continue CC after six earlier failed ovulatory CC cycles. WHAT IS ALREADY KNOWN For women with normogonadotropic anovulation, CC has been a long-standing first-line treatment in conjunction with intercourse or intrauterine insemination (IUI). We recently showed that a switch to gonadotropins increases the chance of live birth by 11% in these women over continued treatment with CC after six failed ovulatory cycles, at a cost of €15 258 per additional live birth. It is unclear whether EMT can be used to identify women who can continue on CC with similar live birth rates without the extra costs of gonadotropins. STUDY DESIGN, SIZE, DURATION Between 8 December 2008 and 16 December 2015, 666 women with CC failure were randomly assigned to receive an additional six cycles with a change to gonadotropins (n = 331) or an additional six cycles continuing with CC (n = 335), both in conjunction with intercourse or IUI. The primary outcome was conception leading to live birth within 8 months after randomisation. EMT was measured mid-cycle before randomisation during their sixth ovulatory CC cycle. The EMT was available in 380 women, of whom 190 were allocated to gonadotropins and 190 were allocated to CC. PARTICIPANTS/MATERIALS, SETTING, METHODS EMT was determined in the sixth CC cycle prior to randomisation. We tested for interaction of EMT with the treatment effect using logistic regression. We performed a spline analysis to evaluate the association of EMT with chance to pregnancy leading to a live birth in the next cycles and to determine the best cut-off point. On the basis of the resulting cut-off point, we calculated the relative risk and 95% CI of live birth for gonadotropins versus CC at EMT values below and above this cut-off point. Finally, we calculated incremental cost-effectiveness ratios (ICER). MAIN RESULTS AND THE ROLE OF CHANCE Mid-cycle EMT in the sixth cycle interacted with treatment effect (P < 0.01). Spline analyses showed a cut-off point of 7 mm. There were 162 women (45%) who had an EMT ≤ 7 mm in the sixth ovulatory cycle and 218 women (55%) who had an EMT > 7 mm. Among the women with EMT ≤ 7 mm, gonadotropins resulted in a live birth in 44 of 79 women (56%), while CC resulted in a live birth in 28 of 83 women (34%) (RR 1.57, 95% CI 1.13–2.19). Per additional live birth with gonadotropins, the ICER was €9709 (95% CI: €5117 to €25 302). Among the women with EMT > 7 mm, gonadotropins resulted in a live birth in 53 of 111 women (48%) while CC resulted in a live birth in 52 of 107 women (49%) (RR 0.98, 95% CI 0.75–1.29). LIMITATIONS, REASONS FOR CAUTION This was a post hoc analysis of a randomised controlled trial (RCT) and therefore mid-cycle EMT measurements before randomisation during their sixth ovulatory CC cycle were not available for all included women. WIDER IMPLICATIONS OF THE FINDINGS In women with six failed ovulatory cycles on CC and an EMT ≤ 7 mm in the sixth cycle, we advise switching to gonadotropins, since it improves live birth rate over continuing treatment with CC at an extra cost of €9709 to achieve one additional live birth. If the EMT > 7 mm, we advise to continue treatment with CC, since live birth rates are similar to those with gonadotropins, without the extra costs. STUDY FUNDING/COMPETING INTEREST(S) The original MOVIN trial received funding from the Dutch Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). C.B.L.A. reports unrestricted grant support from Merck and Ferring. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva, IGENOMIX and Guerbet. All other authors have nothing to declare. TRIAL REGISTRATION NUMBER Netherlands Trial Register, number NTR1449

scholarly journals Comparison of pregnancy outcome between clomiphene citrate and sequential clomiphene citrate+human menopausal gonadotropin in intrauterine insemination

2020 ◽  
Vol 9 (8) ◽  
pp. 3302
Author(s):  
Ankita Singh ◽  
Rohan Palshetkar ◽  
Namrata Singh ◽  
Awyay Rege
Keyword(s):  
Live Birth ◽  
Ovarian Stimulation ◽  
Endometrial Thickness ◽  
Intrauterine Insemination ◽  
Clomiphene Citrate ◽  
Human Menopausal Gonadotropin ◽  
Birth Rates ◽  
Cross Sectional ◽  
Live Birth Rates ◽  
Significant Difference

Background: Intrauterine insemination (IUI) has been widely used as a common treatment for infertile couples. This study compares the sequential clomiphene citrate (CC) treatment with CC and human menopausal gonadotropin (hMG) treatment in women undergoing IUI. Therefore, this study was designed to determine the effects of addition of gonadotropin (CC+hMG) would improve the pregnancy rate in women undergoing IUI. And also compare the sequential CC+hMG treatment with CC treatment in women undergoing IUI.Methods: A cross-sectional study design was conducted at D. Y. Patil Fertility Centre, D.Y Patil Hospital, Navi Mumbai from September 2018 to August 2019. Source populations were all patients who live in Mumbai, Maharashtra, India. A total of 67 patients were enrolled in this study. (It consisted of 67 sub fertile couples undergoing ovarian stimulation for IUI cycles). Results: There was no significant difference between the two studied groups regarding endometrial thickness (8.3±2.1 versus 9.7±2.8, respectively), number of mature follicles on the day of hCG injection (3.3±1.2 versus 3.5±1.1, respectively) and, but there was significant difference between the CC+hMG group and CC group regarding the total dose of gonadotropins used in ovulation induction (305±23.8 versus 655±192; total IU, respectively) p<0.05.Conclusions: Women undergoing IUI, ovarian stimulation CC combined with hMG, significantly improved the pregnancy and live birth rates as compared to that of CC group. In women undergoing ovarian stimulation and IUI, there are no significant differences in pregnancy and live birth rates among the various stimulation protocols.

P-377 Association between antinuclear antibodies and pregnancy prognosis in recurrent pregnancy loss patients

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
H Yoshihara ◽  
M Sugiura-Ogasawara ◽  
T Kitaori ◽  
S Goto
Keyword(s):  
Live Birth ◽  
Pregnancy Loss ◽  
Birth Rate ◽  
Recurrent Pregnancy Loss ◽  
Live Birth Rate ◽  
Negative Group ◽  
Birth Rates ◽  
Positive Group ◽  
Live Birth Rates ◽  
Uterine Anomaly

Abstract Study question Can antinuclear antibody (ANA) affect the subsequent live birth rate in patients with recurrent pregnancy loss (RPL) who have no antiphospholipid antibodies (aPLs)? Summary answer ANA did not affect the pregnancy prognosis of RPL women. What is known already The prevalence of ANA is well-known to be higher in RPL patients. Our previous study found no difference in the live birth rates of ANA-positive and -negative patients who had no aPLs. Higher miscarriage rates were also reported in ANA-positive patients compared to ANA-negative patients with RPL. The RPL guidelines of the ESHRE state that “ANA testing can be considered for explanatory purposes.” However, there have been a limited number of studies on this issue and sample sizes have been small, and the impact of ANA on the pregnancy prognosis is unclear. Study design, size, duration An observational cohort study was conducted at Nagoya City University Hospital between 2006 and 2019. The study included 1,108 patients with a history of 2 or more pregnancy losses. Participants/materials, setting, methods 4D-Ultrasound, hysterosalpingography, chromosome analysis for both partners, aPLs and blood tests for ANA and diabetes mellitus were performed before a subsequent pregnancy. ANAs were measured by indirect immunofluorescence. The cutoff dilution used was 1:40. In addition, patients were classified according to the ANA pattern on immunofluorescence staining. Live birth rates were compared between ANA-positive and ANA-negative patients after excluding patients with antiphospholipid syndrome, an abnormal chromosome in either partner and a uterine anomaly. Main results and the role of chance The 994 patients were analyzed after excluding 40 with a uterine anomaly, 43 with a chromosome abnormality in either partner and 32 with APS. The rate of ANA-positive patients was 39.2 % (390/994) when the 1: 40 dilution result was positive. With a 1:160 dilution, the rate of ANA-positive patients was 3.62 % (36/994). The live birth rate was calculated for 798 patients, excluding 196 patients with unexplained RPL who had been treated with any medication. With the use of the 1 40 dilution, the subsequent live birth rates were 71.34 % (219/307) for the ANA-positive group and 70.67 % (347/491) for the ANA-negative group (OR, 95%CI; 0.968, 0.707-1.326). After excluding miscarriages with embryonic aneuploidy, chemical pregnancies and ectopic pregnancies, live birth rates were 92.41 % (219/237) for the ANA-positive group and 92.04 % (347/377) for the ANA-negative group (0.951, 0.517-1.747). Using the 1:160 dilution, the subsequent live birth rates were 84.62 % (22/26) for the ANA-positive group, and 70.47 % (544/772) for the ANA-negative group (0.434, 0.148-1.273). Subgroup analyses were performed for each pattern on immunofluorescence staining, but there was no significant difference in the live birth rate between the two groups. Limitations, reasons for caution The effectiveness of immunotherapies could not be evaluated. However, the results of this study suggest that it is not necessary. Wider implications of the findings The measurement of ANA might not be necessary for the screening of patients with RPL who have no features of collagen disease. Trial registration number not applicable

scholarly journals Should we continue to measure endometrial thickness in modern-day medicine? The effect on live birth rates and birth weight

2018 ◽  
Vol 36 (4) ◽  
pp. 416-426 ◽  
Author(s):  
Vânia Costa Ribeiro ◽  
Samuel Santos-Ribeiro ◽  
Neelke De Munck ◽  
Panagiotis Drakopoulos ◽  
Nikolaos P. Polyzos ◽  
...  
Keyword(s):  
Birth Weight ◽  
Live Birth ◽  
Endometrial Thickness ◽  
Birth Rates ◽  
Live Birth Rates

scholarly journals Applying growth hormone as an adjuvant to correct poor prognosis outcomes in IVF: Study 2 compares dehydroepiandrosterone

2021 ◽  
Vol 16 (3) ◽  
pp. 164-190
Author(s):  
John Lui Yovich ◽  
Shanthi Srinivasan ◽  
Mark Sillender ◽  
Shipra Gaur ◽  
Philip Rowlands ◽  
...  
Keyword(s):  
Live Birth ◽  
Ovarian Reserve ◽  
Poor Prognosis ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Utilization Rate ◽  
Recurrent Implantation Failure ◽  
Birth Rates ◽  
Live Births ◽  
Live Birth Rates

This retrospective study examines the influence of recombinant growth hormone (rGH) and dehydroepiandrosterone (DHEA) adjuvants on oocyte numbers, embryo utilization and live births arising from 3637 autologous IVF±ICSI treatment cycles undertaken on 2376 women across ten years (2011-2020) within a pioneer Australian facility. Despite using an FSH-dosing algorithm enabling maximal doses up to 450 IU for women with reduced ovarian reserve, younger women had significantly higher mean numbers of oocytes recovered than older women ranging from 11.1 for women <35 years to 9.4 for women aged 35-39 years reducing to 6.5 for women aged 40-44 years and 4.1 for those aged ≥45 years (p<0.0001). Overall, the embryo utilization rate was 48.5% and live birth productivity rate was 35.4 % across all ages and neither rGH nor DHEA showed any benefit on these rates, in fact, those women with nil adjuvants showed the highest live birth rate per initiated cycle (44.94% overall: p<0.0001, and 55.2% for the youngest group: p<0.001). Embryo utilization was increased by rGH in those women aged 40-44 years who had low ovarian reserve (p<0.0001), but this benefit did not translate into any improvement in the live birth rate, in fact those women who did not use adjuvants had the highest overall birth rate (p<0.0001). Similarly, other factors known to cause a poor prognosis, including low IGF-1 profile, recurrent implantation failure, and low oocyte numbers at OPU, showed no improvement in embryo utilization nor in live births from the adjuvants. The relevance of embryo quality was examined on 1135 women whose residual embryos after a single fresh-embryo transfer failed to develop to a suitable grade for cryopreservation. From 1727 cycles such women often displayed an improved embryo utilization rate with both rGH, and with DHEA or combined rGH+DHEA. Even so, live birth rates were not improved by either of the adjuvants excepting young women <35 years using rGH without DHEA (p<0.05). Examining poor prognosis sub-groups, indicated both rGH and DHEA or combined rGH+DHEA consistently improved embryo utilization in those women with low ovarian reserve (p<0.0001), or those with low IGF-1 levels (p<0.0001) or with recurrent implantation failure (p<0.02). All the poor-prognosis sub-groups showed low live birth rates and, notwithstanding the improvements in embryo utilization, the live birth rates were not significantly improved by the adjuvants, albeit the rates were closer to the nil adjuvant groups (not significantly different).

scholarly journals Comparison of the C Umulative Live Birth Rates After One ART Cycle Including All Subsequent Frozen–thaw Cycles in Women Undergoing IVF Using Progestin Primed Ovarian Stimulation Versus Long GnRH Agonist Protocol

2021 ◽  
Author(s):  
Hong Chen ◽  
Zhi qin Chen ◽  
Ernest Hung Yu Ng ◽  
zili sun ◽  
Zheng wang ◽  
...  
Keyword(s):  
Live Birth ◽  
Gnrh Agonist ◽  
Ovarian Reserve ◽  
Ovarian Stimulation ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Stimulation Protocol ◽  
Birth Rates ◽  
Live Birth Rates ◽  
Cumulative Live Birth

Abstract Background: The efficacy and reproductive outcomes of progestin primed ovarian stimulation protocol (PPOS) were previously compared to rarely used ovarian stimulation protocol and also the live birth rate were reported by per embryo transfer rather than cumulative live birth rates (CLBRs). Does the use of PPOS improve the cumulative live birth rates (CLBRs) and shorten time to live birth when compared to long GnRH agonist protocol in women with normal ovarian reserve?Methods: A retrospective cohort study was designed to include women aged<40 with normal ovarian reserve (regular menstrual cycles, FSH <10 IU/L, antral follicle count >5) undergoing IVF from January 2017 to December 2019. The primary outcome was cumulative live birth rates (CLBRs) within 18 months from the day of ovarian stimulation.Results: A total of 995 patients were analyzed. They used either PPOS (n=509) or long GnRH agonist (n=486) protocol at the discretion of the attending physicians. Both groups had almost comparable demographic and cycle stimulation characteristics except for duration of infertility which was shorter in the PPOS group. In the GnRH agonist group 372 cases (77%) completed fresh embryo transfer, resulting into 218 clinical pregnancies and 179 live birth. The clinical pregnancy rate, ongoing pregnancy, and live birth per transfer were 58.6%, 54.0%, 53.0% respectively. In the PPOS, no fresh transfer was carried out. During the study period, the total number of initiated FET cycles with thawed embryos was 665 in the PPOS group and 259 in the long agonist group. Of all FET cycles, a total of 206/662 (31.1%) cycles resulted in a live birth in the PPOS group versus 110/257 (42.8%) in the long agonist group (OR: 0.727; 95% CI: 0.607–0.871; p<0.001) .The implantation rate of total FET cycles was also lower in the PPOS group compared with that in the agonist group 293/1004 (29.2%) and 157/455 (34.5%) (OR: 0.846; 95% CI: 0.721–0.992; p= 0.041). Cumulative live birth rates after one complete IVF cycle including fresh and subsequent frozen embryo cycles within 18 months follow up were significantly lower in the PPOS group compared that in the long agonist group 206/509 (40.5%) and 307/486 (63.2%), respectively (OR: 0.641; 95% CI: 0.565-0.726). The average time from ovarian stimulation to pregnancy and live birth was significantly shorter in the long agonist group compared to the PPOS group (p<0.01) In Kaplan-Meier analysis, the cumulative incidence of ongoing pregnancy leading to live birth was significantly higher in the long agonist compared in the PPOS group(Log rank test, p<0.001). Cox regression analysis revealed stimulation protocol adopted was strongly associated with the cumulative live birth rate after adjusting other confounding factors (OR =1.917 (1.152-3.190), p=0.012) .Conclusion: Progestin primed ovarian stimulation was associated with a lower cumulative live birth rates and a longer time to pregnancy / live birth than the long agonist protocol in women with a normal ovarian reserve.

scholarly journals Letrozole: an emerging array of hope for infertile women

2020 ◽  
Vol 9 (2) ◽  
pp. 891
Author(s):  
Manish Maladkar ◽  
Chitra Tekchandani ◽  
Akshata Karchodi
Keyword(s):  
Live Birth ◽  
Ovulation Induction ◽  
Polycystic Ovary ◽  
Clomiphene Citrate ◽  
Unexplained Infertility ◽  
Birth Rates ◽  
Live Birth Rates ◽  
First Line Therapy ◽  
Estrogenic Action

Ovulation induction has been a major breakthrough in the management of female infertility since many decades. Letrozole, an aromatase inhibitor has been used as a potential therapy for ovulation induction. A large number of clinical evidences have been emerging which cite the beneficial role of Letrozole in conditions like anovulatory infertility, polycystic ovary syndrome (PCOS), unexplained infertility and an incipient role in endometriosis- related infertility with regards to higher live-birth rates. Letrozole is a superior alternative to Clomiphene citrate (CC) which has been used conventionally as ovulation inducer. Clomiphene citrate has certain well-defined disadvantages, whereas Letrozole overcomes these limitations to a reasonable extent. The peripheral anti-estrogenic effect of CC leads to prolonged depletion of estrogens receptors, adversely affecting endometrial growth and development as well as quantity and quality of cervical mucus. Persistent blockade of estrogen receptor leads to CC resistance and is associated with reduced ovulation and pregnancy rates. Available evidences suggest Letrozole is superior to CC owing to the lack of persistent anti-estrogenic action due to its short half- life and lack of action on estrogen receptors. This typically leads to monofollicular growth and also higher live birth rates. The current evidences suggest that Letrozole can be placed as first line therapy for the management of infertility due to PCOS and unexplained infertility.

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