Triggering ovulation with gonadotropin-releasing hormone agonist in in vitro fertilization patients with polycystic ovaries does not cause ovarian hyperstimulation syndrome despite very high estradiol levels.

OBJECTIVE: To determine whether inducing ovulation with a GnRH agonist in patients with polycystic ovaries (PCO) would permit oocyte retrieval without the burden or risk of cancellation, coasting, or ovarian hyperstimulation syndrome (OHSS), thus maintaining pregnancy rates by allowing embryo cryopreservation for transfer in a subsequent cycle. DESIGN: Retrospective observational study. SETTING: Private institution. PATIENT(S): Forty-two women who had previously experienced a controlled ovarian hyperstimulation (COH)/IVF cycle that had to be cancelled because of an elevated risk of OHSS. INTERVENTION(S): Forty-two PCO patients with a previous cancelled IVF cycle were assigned to a second controlled ovarian stimulation with recombinant FSH (75-150 IU/day) + GnRH antagonist (0.25 mg/day). Embryos were cryopreserved and transferred in a later cycle. MAIN OUTCOME MEASURE(S): OHSS, oocyte retrieval, and pregnancy rates. RESULT(S): In the first COH, the cycle had to be cancelled to avoid OHSS because E(2) serum levels were above safety levels (4809.6 +/- 2947.7). However, in the second cycle (ovulation triggered with a GnRH agonist) and independent of E(2) serum levels (4518.5 +/- 2118.85), all PCO patients eventually completed oocyte retrieval and frozen ET. With regard to pregnancy rates, 33% of patients receiving a transfer of a previously frozen embryo were successful. No patient developed OHSS. CONCLUSION(S): Triggering ovulation with a GnRH agonist followed by embryo cryopreservation allows PCO patients to complete a COH/IVF cycle with no cycle cancellation, coasting, or OHSS and, finally, to attain good pregnancy rates.

What next for preimplantation genetic screening? Beyond aneuploidy.

Many published papers suggest a favourable impact of preimplantation genetic screening (PGS) on implantation and pregnancy rates, but more recent randomized studies have not confirmed, or could not conclude, that PGS actually improved implantation rates. Team inexperience in embryo screening has been mentioned as the origin of the discrepancies; thus some clinicians allege a need for more powerful, well-designed, randomized studies performed by specialized teams. However, what if all the contradictory results about the benefits of PGS and implantation were not due to technical problems or team specialization but were biological in origin? The developmental programme of an eight-cell embryo relies on signals of maternal origin retrieved from the cytoplasm to initiate a new transcriptional network that will eventually serve as a filter (checkpoints and apoptosis) for aneuploidy. Thus, the use of PGS with the objective of improving the likelihood of a successful pregnancy based only on nuclear abnormalities (aneuploidies) in an early cleavage stage embryo could be invalid since the information (diagnosis) obtained at the moment of biopsy could be overturned by the transcriptional machinery of the new zygote genome.

No room for cancellation, coasting, or ovarian hyperstimulation syndrome in oocyte donation cycles.

We retrospectively studied 429 IVF donor cycles in which ovulation was triggered with either hCG (175 cycles) or GnRH agonist (254 cycles). Of the donors in whom ovulation was triggered with hCG, 3.2% developed symptoms of moderate (2.2%) or severe (1%) ovarian hyperstimulation syndrome, while none of the IVF donor cycles that were triggered with the GnRH agonist presented ovarian hyperstimulation syndrome, needed coasting, or were cancelled.

Multifollicular recruitment in combination with gonadotropin-releasing hormone antagonist increased pregnancy rates in intrauterine insemination cycles.

OBJECTIVE: To determine whether including a GnRH antagonist in controlled ovarian stimulation-intrauterine insemination cycles would increase pregnancy rates. DESIGN: Prospective randomized study. SETTING: Private reproductive medicine clinic in Spain. PATIENT(S): Three hundred sixty-seven women with primary or secondary infertility. INTERVENTION(S): Patients were randomly assigned to controlled ovarian stimulation with recombinant FSH (75-150 IU/d) alone (controls, n = 183) or with recombinant FSH (75-150 IU/d) + the GnRH antagonist (0.25 mg/d), initiated when the recruited follicles were >or=16 mm (n = 184). A single insemination was performed, 36-38 hours after hCG (5,000 IU, IM), in both groups. MAIN OUTCOME MEASURE(S): Follicular recruitment, pregnancy rates. RESULT(S): Numbers of mature follicles (2.4 +/- 1.3 vs. 1.3 +/- 1.09) and clinical pregnancy rates (23% vs. 11%) were statistically significantly higher in patients who were treated with GnRH antagonist than in those who were in the control group. The pregnancy rate was only higher in the antagonist group if more than one follicle sized >or=18 mm was present on the day that the hCG was given. A similar number of twin pregnancies occurred in both groups: two in the antagonist group and three in the control group. The antagonist group also had one triplet gestation. CONCLUSION(S): Adding GnRH antagonist to controlled ovarian stimulation-intrauterine insemination cycles significantly increases pregnancy rates in multifollicular, but not monofollicular, cycles.

Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates.

OBJECTIVE: To evaluate the implant capacity of embryos derived from oocytes matured with a bolus of GnRH agonist. DESIGN: Donors were randomly assigned to a protocol using either GnRH agonist or recombinant (r) hCG to trigger ovulation. Analysis of variance, Student t test, and Fisher exact test were used where appropriate. SETTING: Private clinical setting. PATIENT(S): Young voluntary donors receiving GnRH agonist (n = 30) or rhCG (n = 30). Eighty-nine patients received oocytes. INTERVENTION(S): Controlled ovarian stimulation was carried out with GnRH antagonist and FSH/LH in a step-down protocol. Donors received a single bolus of GnRH agonist (0.2 mg) or rhCG (250 microg). The endometrial tissue of recipient patients was prepared with oral E(2) and P. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates and ovarian hyperstimulation syndrome (OHSS) in an IVF donor program. RESULT(S): No significant differences in the number of retrieved oocytes (327 vs. 288), MII oocytes (70% vs. 76%), fertilization (80% vs. 65%,), pregnancy/transfer (55% vs. 59%), and implantation rates (29% vs. 32%) were found between recipients whose embryos originated from donors in whom final oocyte maturation was triggered with GnRH agonist and those whose donors received hCG. Significant differences in luteal phase length (4.16 + 0.70 days vs. 13.63 + 2.12 days) and in OHSS (0/30 vs. 5/30) were seen between donors ovulated with the agonist and the donors in whom ovulation was triggered with hCG. CONCLUSION(S): In controlled ovarian stimulation IVF donor cycles, GnRH agonists trigger ovulation and induce luteolysis but do not compromise embryo implantation capacity.

Luteinizing hormone supplementation increases pregnancy rates in gonadotropin-releasing hormone antagonist donor cycles.

OBJECTIVE: To determine whether LH supplementation improved pregnancy and implantation rates in GnRH antagonist donor cycles. DESIGN: Donors were randomly assigned to a protocol using GnRH antagonist (GnRH-a) alone or GnRH-a + recombinant LH. Analysis of variance, Student's t-test and Fisher's exact test were used where appropriate. SETTING: Private clinical setting. PATIENT(S): Young voluntary donors with antagonist (n = 20) and antagonist + LH (n = 22). Fifty-five patients received oocytes. INTERVENTION(S): Donors received the GnRH-a (Cetrorelix, 0.25 mg/day) alone or in combination with recombinant LH (75 IU/day). Ovulation induction was carried out with recombinant FSH in a step-down protocol. The endometrial tissue of recipient patients was prepared with oral E(2) and P. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates in a donor program. RESULT(S): A significant increase in MII oocyte (80% vs. 71%), fertilization rates (83% vs. 71%), G1 embryos (17% vs. 3%), and implantation rates (35% vs. 15%), were found in recipients whose embryos originated from donors receiving GnRH-a + recombinant LH as compared to donors receiving GnRH-a alone. Estradiol levels, pregnancy/transfer and clinical pregnancies were lower (not significant) in donors treated with the GnRH-a alone vs. those receiving the recombinant LH-supplemented GnRH-a. CONCLUSION(S): The LH supplementation improved the possibilities of gestation for recipients whose embryos originated from GnRH-a-treated donors.