Mild ovarian stimulation for IVF

Background This large prospective, randomized study was designed to compare the "mild" protocol with clomiphene citrate, low-dose gonadotropins and a GnRH-antagonist (CC/Gn/GnRH-ant protocol) with the "long" protocol with a GnRH-agonist and high-dose Gn for the controlled ovarian hyperstimulation (COH) of patients with expected poor ovarian responsiveness undergoing IVF. Materials and Methods A total of 695 women with clinical, endocrine and ultrasound characteristics suggesting a low ovarian reserve and a poor responsiveness to COH were recruited and randomly assigned to receive the CC/Gn/ GnRH-ant "mild" protocol (mild group, n=355) or the "long" protocol with high-dose Gn (long group, n=340). Results The "mild" stimulation led to significantly shorter follicular phase, lower consumption of exogenous Gn and lower peak estradiol level than the "long" regimen. With the "long" protocol, significantly less cycles were cancelled due to the lack of ovarian response; further, it obtained significantly more oocytes, more mature oocytes, more embryos, and a thicker endometrium. As for the final IVF outcome, however, the two stimulation regimens obtained comparable implantation rate, clinical pregnancy rate, and ongoing pregnancy rate at 12 weeks. Conclusions In conclusion, the "mild" CC/Gn/GnRH-ant stimulation protocol is a valid alternative to the long protocol with high Gn dose as it obtains a comparable success rate and requires significantly less medications, with an obvious economical advantage.

Section: Introductionmentioning

confidence: 99%

“Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial

Revelli

Chiadò

Dalmasso³

et al. 2014

“…Very recent randomized controlled trials have failed to show any benefit by adopting time lapse technology over morphology in improving pregnancy and delivery rates [13,14]. Fourth, we can consider modifying our protocols of ovarian stimulation to avoid the production of too many oocytes, which, as demonstrated here and in previous studies, may not lead to more live births, but to increased BEmbryo Wastages.M inimal stimulation or natural IVF cycles have been associated with improved egg quality and reduced aneuploidy rates [37][38][39]. Additionally, a reduction in the amount of medication used for stimulation would reduce the risk of ovarian hyperstimulation syndrome for high responders, and possibly be a more cost-effective strategy for poor responders [40,41] and reduce the rates of oocyte aneuploidy [42].…”

Section: Discussionmentioning

confidence: 99%

Embryo wastage rates remain high in assisted reproductive technology (ART): a look at the trends from 2004–2013 in the USA

Ghazal¹,

Patrizio²

2016

This work examined the trend in Bembryo wastager ates after ART in USA and its relationship to the number of embryos transferred, live born infants delivered across patient age, and the yearly percentage of embryos wasted. The data were obtained from the US-clinics SART databank for the years 2004-2013. A total of 1,808,082 non-donor embryos were transferred in 748,394 fresh cycles resulting in 358,214 liveborn. During the years of analysis, the mean number of embryos transferred has progressively decreased leading to an overall significant decrease in Embryo Wastage rates (83.2 to 76.5%, p < 0.001) while the percentage of transfers leading to a live born increased (24.8 to 27.8%, p = 0.002). Embryo Wastage negatively correlated with percentage of transfers resulting in live birth (p = 0.001), and the average number of embryos transferred positively correlated with the percentage of embryos wasted (p < 0.001). The overwhelming majority of embryos transferred still do not result into a live birth confirming that only few embryos per ART cycle are competent. The overall BEmbryo Wastage^rates have consistently decreased from a high of 90% in 1995 to a rate of 76.5% in 2013. Transferring fewer embryos particularly at the blastocyst-stage and improved methods of embryo selection may further decrease BEmbryo Wastage^rates.

“…The late-start, "mild" stimulation COS regimens are subjectively better tolerated (less abdominal discomfort and swelling) (15), shorter, and consequently probably cheaper than standard protocols (2,3,17). In comparison to the "classical" COS, they compensate the slightly reduced "per attempt" effectiveness with the improved tolerability, that lowers the drop-out rate and finally increases the number of attempts, leading to a comparable cumulative yearly success rate (18).…”

Section: Discussionmentioning

confidence: 99%

“…Further, GnRH-antagonists allowed to develop the so-called "mild" or "minimal" stimulation COS regimens, in which the initial follicular recruitment is accomplished by endogenous gonadotropins, and exogenous Gn are administered only from day 4-5 of the cycle onward (1)(2)(3)(4). Aim of the "mild" COS is to obtain a patient-friendly treatment, with higher tolerability and without worsening IVF outcome.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of late-start Corifollitropin-alfa administration for controlled ovarian hyperstimulation in IVF: a cohort, case–control study

Revelli

Pittatore

Casano

et al. 2015

Objective To investigate efficacy and safety of a controlled ovarian stimulation (COS) protocol in which a single dose of Corifollitropin-alfa (CFα) was administered on day 4 of a GnRH-antagonist cycle. Design Cohort case-control study. Setting University Hospital. Patients One hundred twenty-two normally cycling women expected to be normal responders to COS. Interventions In 61 patients, CFα (100-150 μg) was injected subcutaneously on day 4 of a spontaneous menstrual cycle; a GnRH-antagonist was added from day 8 (fixed protocol; 0.25 mg/day). If needed to complete follicular maturation, recombinant FSH (rFSH) daily injections (150/200 IU/day) were given from day 11. A control group of 61 matched women was stimulated with daily subcutaneous injections of rFSH (100-150 U/day) from day 4 of the cycle, and received GnRH-antagonist (0.25 mg/day) from day 8. IVF or ICSI was performed according to the sperm characteristics, and 1-2 embryos were transferred in utero under US guidance on day 2.Main outcome measures Number of retrieved cumulusoocyte complexes (COCs), clinical pregnancy rate (PR), implantation rate (IR), ongoing PR at 10 weeks, number of injections/cycle, ovarian hyperstimulation syndrome (OHSS) rate.Results No cycle was cancelled and the mean number of retrieved COCs was comparable in patients and controls. About 60 % of CF-alfa treated women had no need of daily rFSH addition, and the mean number of injections/cycle was significantly lower in the CF-alfa group than in controls (p<0.05). The ongoing PR/transfer was 36.8 % in CF-alfa group and 37.5 % in controls. No patient developed severe OHSS, and the incidence of moderate OHSS was similar in cases and controls. Conclusions CFα may be started on day 4 of the cycle obtaining results comparable to those of a COS using day 4-start daily rFSH, with significantly less injections and a similar risk of OHSS.