Ovulation Induction with Oral Agents for Women 38 Years and Older Yields Low Live Birth Rates with Intrauterine Insemination Regardless of Ovarian Reserve

2015 ◽  
Vol 103 (2) ◽  
pp. e11
Author(s):  
E. Barnard ◽  
Z. Khan ◽  
D. Morbeck ◽  
J. Jensen
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Cobo

Abstract text The challenge of cryopreserve, store for prolonged period, and successfully implant the female gamete is nowadays feasible thanks to vitrification. The technology that was initially validated in oocyte recipients is currently applied to a vast population, including women at risk of losing their ovarian function due either to iatrogenic causes as occurs in cancer patients, or due to the natural depletion of the ovarian reserve as a result of age related fertility decline. That is the case of a growing population of women who wish to postpone childbearing and decide on oocyte vitrification as a means of fertility preservation (FP). At present, there is a growing body of evidence regarding the use of vitrified oocytes by many women under different indications, which makes it possible to evaluate the approach from different scenarios. So that vitrification can be evaluated in terms on survival rates, embryo development and the rate at which vitrified oocytes develop into live-born children in IVF cycles using vitrified oocytes which were initially stored due to different reasons. The effects of vitrification at the subcellular level and its impact on oocyte competence is of interest in the evaluation of the efficacy of the technology. Some studies have indicated that vitrification may affect ultrastructure, reactive oxygen species (ROS) generation, gene expression, and epigenetic status. However, it is still controversial whether oocyte vitrification could induce DNA damage in the oocytes and the resulting early embryos. Recent studies show that oocytes survival and clinical outcome after vitrification can be impaired by patients’ age and the clinical indication or the reason for vitrification. These studies show that age at oocyte retrieval strongly affects the survival and reproductive prognosis. In our experience, oocyte survival, pregnancy and cumulative live birth rates are significantly higher when patients are aged 35 years or younger versus patients older than 35 years at oocyte retrieval. Therefore, elective-FP patients should be encouraged to decide at young ages to significantly increase their chances of success. There is also evidence that the reason for vitrification is associated to the success rates. Poorer reproductive outcome was reported in cancer patients, low responders and endometriosis patients when compared to healthy women in age matching groups. Moreover, there are certain individualities linked to specific populations, as occurs when endometriosis patients had cystectomy earlier than the oocyte retrieval for FP. These women achieved lower success rates as compared to non-operated age matching counterparts. In this case, the lower cumulative live birth rates observed in operated women are, most probably, due to the smaller number of oocytes available, as a consequence of the detrimental effect of the surgery on the ovarian reserve. In this regard, several reports show that the number of oocytes available per patient is another variable closely related to the outcome in all populations using vitrified oocytes after FP. Thus, a significant improvement in the cumulative live birth rates can be achieved by adding a few oocytes, especially in healthy young patients. Different populations using vitrified oocytes under several indications achieve differential results in terms of pregnancy rates, when calculated in overall. Nonetheless, when the calculations for the cumulative probability of achieving a baby are made according the number of oocytes used per patient belonging to the same group of age, the results become comparable between different populations, as shown by the comparison between elective freezers versus endometriosis patients. Undoubtedly, vitrification can be recognized as one of the latest brakethrough in the ART field, but certainly the next step forward would be the successfull automatization of the vitrification and warming processes to achieve fully consistency among different laboratories.


2021 ◽  
Vol 16 (3) ◽  
pp. 164-190
Author(s):  
John Lui Yovich ◽  
Shanthi Srinivasan ◽  
Mark Sillender ◽  
Shipra Gaur ◽  
Philip Rowlands ◽  
...  

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).


2021 ◽  
Author(s):  
Hong Chen ◽  
Zhi qin Chen ◽  
Ernest Hung Yu Ng ◽  
zili sun ◽  
Zheng wang ◽  
...  

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.


2021 ◽  
Vol 10 (22) ◽  
pp. 5247
Author(s):  
Marie-Madeleine Dolmans ◽  
Camille Hossay ◽  
Thu Yen Thi Nguyen ◽  
Catherine Poirot

Chemotherapy, pelvic radiotherapy and ovarian surgery have known gonadotoxic effects that can lead to endocrine dysfunction, cessation of ovarian endocrine activity and early depletion of the ovarian reserve, causing a risk for future fertility problems, even in children. Important determinants of this risk are the patient’s age and ovarian reserve, type of treatment and dose. When the risk of premature ovarian insufficiency is high, fertility preservation strategies must be offered to the patient. Furthermore, fertility preservation may sometimes be needed in conditions other than cancer, such as in non-malignant diseases or in patients seeking fertility preservation for personal reasons. Oocyte and/or embryo vitrification and ovarian tissue cryopreservation are the two methods currently endorsed by the American Society for Reproductive Medicine, yielding encouraging results in terms of pregnancy and live birth rates. The choice of one technique above the other depends mostly on the age and pubertal status of the patient, and personal and medical circumstances. This review focuses on the available fertility preservation techniques, their appropriateness according to patient age and their efficacy in terms of pregnancy and live birth rates.


2020 ◽  
Vol 35 (6) ◽  
pp. 1319-1324
Author(s):  
E M Bordewijk ◽  
N S Weiss ◽  
M J Nahuis ◽  
J Kwee ◽  
A F Lambeek ◽  
...  

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 &lt; 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 &gt; 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 &gt; 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 &gt; 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


Author(s):  
Manish Maladkar ◽  
Chitra Tekchandani ◽  
Akshata Karchodi

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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