Are commercial warming kits interchangeable for vitrified human blastocysts? Further evidence for the adoption of a Universal Warming protocol.

PURPOSE: To study whether a new combination of different warming kits is clinically effective for vitrified human blastocysts. METHODS: This is a longitudinal cohort study analysing two hundred fifty-five blastocysts warming cycles performed between January and October 2018. Embryos were vitrified using only one brand of ready-to-use kits (Kitazato), whereas the warming procedure was performed with three of the most widely used vitrification/warming kits (Kitazato, Sage and Irvine) after patient stratification for oocyte source. The primary endpoint was survival rate, while the secondary endpoints were clinical pregnancy, live birth and miscarriage rates. RESULTS: We observed a comparable survival rate across all groups of 100% (47/47) in KK, 97.6% (49/50) in KS, 97.6% (41/42) in KI, 100% (38/38) in dKK, 100% (35/35) in dKS and 100% (43/43) in dKI. Clinical pregnancy rates were also comparable: 38.3% (18/47) in KK, 49% (24/49) in KS, 56.1% (23/ 41) in KI, 47.4% (18/38) in dKK, 31.4% (11/35) in dKS and 48.8% (21/ 43) in dKI. Finally, live birth rates were 29.8% (14/47) in KK, 36.7% (18/49) in KS, 46.3% (19/41) in KI, 36.8% (14/38) in dKK, 25.7% (9/35) in dKS and 41.9% (18/43) in dKI, showing no significant differences. CONCLUSION: This study confirmed the efficacy of applying a single warming protocol, despite what the "industry" has led us to believe, supporting the idea that it is time to proceed in the cryopreservation field and encouraging embryologists worldwide to come out and reveal that such a procedure is possible and safe.

Controlled Ovarian Stimulation with recombinant-FSH plus recombinant-LH vs. human Menopausal Gonadotropin based on the number of retrieved oocytes: results from a routine clinical practice in a real-life population.

BACKGROUND: The association of recombinant FSH (rFSH) plus recombinant LH (rLH) is currently used for Controlled Ovarian Stimulation (COS) in human IVF, but its efficacy has, to date, not yet been compared to that of human Menopausal Gonadotropin (hMG), the FSH + LH activity-containing urinary drug. METHODS: Eight hundred forty-eight (848) IVF patients classified as expected "poor" or "normal" responders according to antral follicle count (AFC) and basal (day 3) FSH were treated with rFSH + rLH (2:1 ratio, n = 398, Group A) or hMG (n = 450, Group B). Data were collected under real-life practice circumstances and the pregnancy rate with fresh embryos was calculated by stratifying patients according to the number of retrieved oocytes (1-2, 3-4, 5-6, 7-8, >8). RESULTS: Overall, the pregnancy rate in both groups progressively improved according to the number of oocytes retrieved. When comparing patients within the same subgroup of oocyte yield, Group A and B showed a comparable outcome up to the reported highest yield (>8). When more than 8 oocytes were available, Group A had a significantly better pregnancy rate outcome. Patients' characteristics did not significantly differ between the two groups and the better outcome in the best responding patients in Group A was confirmed by a multivariable logistic regression analysis, that showed that both the use of rFSH + rLH and the total number of retrieved oocytes increased the probability of pregnancy with odd ratio (OR) of 1.628 and 1.083, respectively. CONCLUSIONS: When comparing patients with the same number of retrieved oocytes under real-life circumstances, the association of rFSH + rLH results in a significantly higher pregnancy rate than hMG when more than 8 oocytes are retrieved. The reason(s) for this are unknown, but a more favorable effect on oocyte quality and/or endometrial receptivity could be involved.

MILD ovarian stimulation with GnRH-antagonist vs. long protocol with low dose FSH for non-PCO high responders undergoing IVF: a prospective, randomized study including thawing cycles.

OBJECTIVE: To compare the effectiveness of two stimulation protocols in non-polycystic ovary (PCO) high responders undergoing in vitro fertilization (IVF). DESIGN: Prospective randomized trial. SETTING: A Reproductive Medicine and IVF Unit of a University Hospital and a private IVF Clinic. METHODS: Four hundred-and-twelve normoovulatory women with good ovarian responsiveness were randomized to receive either the "mild" (FSH 150 IU/day from day 4 of a spontaneous cycle followed by GnRH-antagonist from day 8; n = 205) or the "long" (FSH 150 IU/day; n = 207) stimulation protocol. The outcome of these two regimens was compared including "fresh" and thawing cycles. RESULTS: The total FSH dose and the peak estradiol level were significantly lower in the "mild" protocol, whereas the retrieved oocytes, fertilization rate, number and quality of embryos, pregnancy and implantation rates, cumulative "fresh plus thaw" success rate, and incidence of severe ovarian hyperstimulation syndrome were comparable with the two regimens. CONCLUSIONS: In young, normoovulatory patients with good ovarian responsiveness undergoing IVF the "mild" stimulation protocol has effectiveness and risks comparable to the "long" protocol with low FSH starting dose, even when thawing cycles are included in the comparison.

Outcome of in vitro fertilization in patients with proven poor ovarian responsiveness after early vs. mid-follicular LH exposure: a prospective, randomized, controlled study.

OBJECTIVE: To compare early vs. mid-follicular exposure to LH in patients with poor ovarian responsiveness undergoing in vitro fertilization (IVF). DESIGN: Prospective, randomized, controlled trial. SETTING: University Hospital, University-affiliated private Clinic. PATIENTS: Five hundred-thirty women with poor ovarian responsiveness during the first IVF cycle, undergoing their second IVF attempt. INTERVENTIONS: In a GnRH-analogue long protocol, ovarian stimulation with recombinant FSH (300 IU/day) plus randomly assigned addition of recombinant LH (150 IU/day) from day 1 (early LH exposure; n = 264) or from day 7 (late LH exposure; n = 266). MAIN OUTCOME MEASURE(S): Primary outcome was the number of oocytes retrieved. Secondary outcomes were: cancellation rate, total gonadotropin dose, duration of ovarian stimulation, number of embryos available for transfer, pregnancy rate per started cycle, per OPU and per embryo transfer, implantation rate, delivered/ongoing pregnancy rate. RESULTS: Apart from the totally administered LH dose, that was significantly higher in the group receiving it from day 1, all parameters related to IVF outcome were non significantly different in the two groups. CONCLUSIONS: Adding LH to FSH from day 1 or from day 7 of ovarian stimulation in a GnRH-agonist long protocol exerts comparable effects on IVF outcome in poor responders.

Ovarian endometriomas and IVF: a retrospective case-control study.

We performed this retrospective case-control study analyzing 428 first-attempt in vitro fertilization (IVF) cycles, among which 254 involved women with a previous or present diagnosis of ovarian endometriosis. First, the results of these 254 cycles were compared with 174 cycles involving patients with proven non-endometriotic tubal infertility having similar age and body mass index. Women with ovarian endometriosis had a significantly higher cancellation rate, but similar pregnancy, implantation and delivery rates as patients with tubal infertility. Second, among the women with ovarian endometriosis, the women with a history of laparoscopic surgery for ovarian endometriomas prior to IVF and no visual endometriosis at ovum pick-up (n = 112) were compared with the non-operated women and visual endometriomas at ovum pick-up (n = 142). Patients who underwent ovarian surgery before IVF had significantly shorter period, lower antral follicle count and required higher gonadotropin doses than patients with non-operated endometriomas. The two groups of women with a previous or present ovarian endometriosis did, however, have similar pregnancy, implantation and live birth rates. In conclusion, ovarian endometriosis does not reduce IVF outcome compared with tubal factor. Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins.

A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments.

BACKGROUND: Anti-thyroid antibodies (ATA), even if not associated with thyroid dysfunction, are suspected to cause poorer outcome of in vitro fertilization (IVF). METHODS: We retrospectively analyzed: (a) the prevalence of ATA in euthyroid infertile women, (b) IVF outcome in euthyroid, ATA+ patients, and (c) the effect of adjuvant treatments (levothyroxine alone or associated with acetylsalicylic acid and prednisolone) on IVF results in ATA+ patients. One hundred twenty-nine euthyroid, ATA+ women undergoing IVF were compared with 200 matched, ATA-controls. During IVF cycle, 38 ATA+ patients did not take any adjuvant treatment, 55 received levothyroxin (LT), and 38 received LT +acetylsalicylic acid (ASA)+prednisolone (P). RESULTS: The prevalence of ATA among euthyroid, infertile patients was 10.5%, similar to the one reported in euthyroid women between 18 and 45 years. ATA+ patients who did not receive any adjuvant treatment showed significantly poorer ovarian responsiveness to stimulation and IVF results than controls. ATA+ patients receiving LT responded better to ovarian stimulation, but had IVF results as poor as untreated ATA+ women. Patients receiving LT+ASA+P had significantly higher pregnancy and implantation rates than untreated ATA+ patients (PR/ET 25.6% and IR 17.7% vs. PR/ET 7.5% and IR 4.7%, respectively), and overall IVF results comparable to patients without ATA (PR/ET 32.8% and IR 19%). CONCLUSION: These observations suggest that euthyroid ATA+ patients undergoing IVF could have better outcome if given LT+ASA+P as adjuvant treatment. This hypothesis must be verified in further randomized, prospective studies.