Geoffrey Sher

Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development

OBJECTIVE To evaluate the effects of vaginally administered sildenafil on endometrial thickness and IVF outcome in a large cohort of infertile women with poor endometrial development. DESIGN Retrospective cohort analysis. SETTING Private practice setting. PATIENT(S) A cohort of 105 infertile women aged <40 years, with normal ovarian reserve and at least two consecutive prior IVF failures attributed to inadequate endometrial development. INTERVENTION(S) Patients underwent IVF using a long GnRH-a protocol with the addition of sildenafil vaginal suppositories (25 mg, 4 times per day) for 3-10 days. MAIN OUTCOME MEASURE(S) Peak endometrial development, pregnancy, and implantation rates. RESULT(S) Of 105 patients, 73 (70%; Group A), attained an endometrial thickness of >/=9 mm, whereas 32 (30%; Group B) did not. Implantation and ongoing pregnancy rates were significantly higher for Group A (29% and 45%) than for Group B (2% and 0). Of 11 women in Group B who had embryos transferred in that cycle, only one conception occurred, which resulted in a miscarriage. In Group B, 59% of women had a history of endometritis, compared with 44% in Group A. CONCLUSION(S) Vaginal administration of sildenafil enhanced endometrial development in 70% of patients studied. High implantation and ongoing pregnancy rates were achieved in a cohort with a poor prognosis for success. Previous endometritis may decrease the response to sildenafil.

Mock embryo transfer in early luteal phase, the cycle before in vitro fertilization and embryo transfer: a descriptive study *

OBJECTIVE To investigate visually the uterine retention or sequestration of boluses of radiopaque dye, mimicking embryo transfer (ET). DESIGN During the cycle before in vitro fertilization (IVF) and ET, patients underwent a mock ET of 40 microL of radiopaque dye into the uterine cavity. The patient was positioned supine for retroverted or axial and knee chest for anteverted uteri. The position of the dye at injection, during and after catheter removal, and during patient roll over and standing was monitored. SETTING Treatment of infertility in a private practice. PATIENTS Thirty-four IVF patients. INTERVENTIONS During the cycle before IVF/ET, patients underwent a mock ET using a bolus of 40 microL of radiopaque dye. MAIN OUTCOME MEASURES Planned before visual observation began. RESULTS The dye remained primarily in the uterine cavity in only 68% (optimum ET position is knee chest for anteverted and supine for retroverted or axial uterus) and 48% (nonoptimum position is supine for anteverted uterus) at mock ET; in those groups, a 33% clinical pregnancy rate (PR) per retrieval resulted. Dye motility into the fallopian tube(s), cervix, and/or vagina is 38.2%, 8.8%, and 11.8%, respectively. CONCLUSIONS If the mock ET had been the actual ET, 32% (optimum ET position) and 52% (nonoptimum ET position) of all patients would have lost their opportunity for pregnancy as a result of the ET procedure. Our 33% PR per retrieval among those patients who retained the dye in utero is more consistent with our expectations, given the advanced technologies of IVF/ET today.

In vitro sperm capacitation and transcervical intrauterine insemination for the treatment of refractory infertility: Phase I

Fourteen couples with long-standing infertility, associated with cervical mucus insufficiency, male subfertility, or unexplained infertility, participated in a therapeutic trial. The female partners, who were all ovulatory, were given human menopausal gonadotropin from day 2 of the menstrual cycle (controlled ovarian hyperstimulation). When plasma estradiol concentrations reached 1000 to 2000 pg/ml, human chorionic gonadotropin was given. Approximately 32 hours and again 70 hours thereafter, a masturbation specimen of the husbands sperm was capacitated in vitro and inseminated transcervically into the uterine cavity. Five women (35%) conceived following a single cycle of treatment. Four of the pregnancies are currently progressing normally; one ended in a spontaneous miscarriage in the early first trimester. The potential role of in vitro sperm capacitation and transcervical intrauterine insemination in the treatment of refractory infertility unrelated to female organic pelvic disease is discussed.

The Selective Use of Heparin/Aspirin Therapy, Alone or in Combination with Intravenous Immunoglobulin G, in the Management of Antiphospholipid Antibody-Positive Women Undergoing In Vitro Fertilization

PROBLEM: The effect of mini‐dose heparin/aspirin (H/A) alone vs. combined intravenous immunoglobulin G (IVIg) and H/A on in vitro fertilization (IVF) birthrates in women who test seropositive for antiphospholipid antibodies (APA+) was evaluated, as was the question of whether outcome is influenced by the gammaglobulin isotype(s) or the phospholipid (PL) epitope(s) to which the APAs are directed.

A Rational Basis for the Use of Combined Heparin/Aspirin and IVIG Immunotherapy in the Treatment of Recurrent IVF Failure Associated with Antiphospholipid Antibodies

PROBLEMS: 1) Does the administration of heparin and aspirin (H/A) in combination with intravenous immunoglobulin G (IVIG) improve in vitro fertilization (IVF) implantation and birth rates in patients with recurrent IVF failures? 2) Is the effect of such treatment related to the antiphospholipid antibody (APA) status of the patients concerned?

Genetic analysis of human embryos by metaphase comparative genomic hybridization (mCGH) improves efficiency of IVF by increasing embryo implantation rate and reducing multiple pregnancies and spontaneous miscarriages

OBJECTIVE To assess the benefit of selecting blastocysts for cryotransfer based upon prior comparative genomic hybridization (CGH) karyotyping of blastomeres derived from their cleaved embryos of origin. Implantation and birth rates per transfer of previtrified CGH-tested blastocysts were compared with those following the transfer of nonCGH-tested fresh and warmed embryos. DESIGN In vitro studies. SETTING Private infertility clinic. PATIENT(S) Women undergoing infertility treatment. INTERVENTION(S) Three groups of women with similar clinical and demographic characteristics were compared. Group A underwent transfer of warmed blastocysts derived from CGH-normal day 3 embryos. Group B underwent embryo transfer of warmed blastocysts derived from nonkaryotyped vitrified embryos. Group C underwent fresh transfers with non-CGH-tested blastocysts. MAIN OUTCOME MEASURE(S) Implantation and birth rates per embryo after the cryotransfer of CGH-tested blastocysts. RESULT(S) The birth rate per transferred blastocyst in group A was 48%, versus 15% for group B and 19% for group C. The birth rate per embryo transfer was 60% for group A, and 33% for group B and 36% for group C. The miscarriage rate was 4% in group A, 8% in group B, and 12% in group C. CONCLUSION(S) The transfer of previously vitrified blastocysts derived from CGH-normal embryos significantly improves implantation and birth rates per embryo transferred and reduces the miscarriage rate. Vitrification does not compromise this enhancement.

Vitrification of human embryos subjected to blastomere biopsy for pre-implantation genetic screening produces higher survival and pregnancy rates than slow freezing

PurposeCryopreservation of blastocysts, especially those subjected to the trauma due to blastomere biopsy for the purposes of pre-implantation genetic screening (PGS), requires significant optimization. Laboratory and clinical outcomes were compared to determine the effect of two different cryopreservation techniques on the development of human pre-implantation embryos that underwent blastomere biopsy and blastocoel drainage prior to cryopreservation.DesignRetrospective clinical study.Patient(s)Women who requested cryotransfer of supernumerary blastocysts were analyzed by FISH.ResultsThe main outcome measures were post-thaw survival (SR), pregnancy (PR), and implantation (IR). The SR of slowly frozen blastocysts was 83% compared to 97% for vitrified blastocysts. In 160 cases where biopsied embryos were cryotransferred, the results for slowly frozen versus vitrified blastocysts were: SR (71% vs. 95%), PR (23% vs. 37%), and IR (26% vs. 36%, P < 0.05), respectively.ConclusionThe results revealed that vitrified blastocysts provided higher SR, PR and IR as compared to slowly frozen counterparts.

The effect of the biochemical marker soluble human leukocyte antigen G on pregnancy outcome in assisted reproductive technology—a multicenter study

OBJECTIVE To determine whether the presence of soluble human leukocyte antigen G (sHLA-G) affects implantation and pregnancy outcomes in vitro. DESIGN A multicenter retrospective study. SETTING Six certified in vitro fertilization (IVF) units. PATIENT(S) Embryos obtained from 2,040 patients from six different IVF clinics. INTERVENTION(S) Soluble HLA-G determination on day-2 embryos after intracytoplasmic sperm injection, with embryos transferred on day 3 using the sHLA-G data. MAIN OUTCOME MEASURE(S) Ongoing pregnancy rate (10- to 12-week ultrasound finding). RESULT(S) All embryos were individually cultured, and a chemiluminescence enzyme-linked immunosorbent assay was used to detect the presence of sHLA-G in the culture medium surrounding the embryos. Embryos were selected based on a positive sHLA-G result and a graduated embryo scoring (GES) score >70, or on embryo morphology if the test was negative. In all centers, a positive sHLA-G result was associated with an increase in the odds of an ongoing pregnancy. The incidence of an ongoing pregnancy was 2.52 times greater in embryos transferred on day 3 with a positive sHLA-G test result than the incidence of an ongoing pregnancy in embryos with a negative sHLA-G test result. CONCLUSION(S) Data from this multicenter study confirm that sHLA-G expression is a valuable noninvasive embryo marker to assist in improving pregnancy outcomes, with the theoretical potential to reduce multiple pregnancies.

The development of a successful non-university-based ambulatory in vitro fertilization/embryo transfer program: Phase I

Most of the current in vitro fertilization and embryo transfer (IVF-ET) programs are university-based. The establishment of a successful ambulatory IVF program in association with a busy, two-man general obstetrics-gynecologic practice is described. Seventy-one infertile couples were screened between February 1 and October 15, 1983. Forty-three couples were judged eligible for IVF-ET. Forty-three women underwent a single attempt at ET. The first 13 of these women underwent controlled ovarian hyperstimulation (COH) with 150 mg clomiphene citrate and human chorionic gonadotropin (hCG), and the remaining 30 underwent COH with human menopausal gonadotropin (hMG) and hCG. One of the 13 patients who underwent COH with clomiphene citrate conceived but subsequently miscarried early in the first trimester, for an 8% pregnancy rate. There were 12 pregnancies among the 30 patients who received hMG and hCG, for a 40% pregnancy rate. Only three of these pregnancies miscarried in the early first trimester, and three of the nine viable pregnancies are twin gestations. The possible factors responsible for the high pregnancy rate with IVF-ET, using COH with hMG and hCG, are discussed, and the feasibility of its performance in a well-controlled, non-university program is demonstrated.

Embryo selection criteria based on morphology VERSUS the expression of a biochemical marker (sHLA-G) and a graduated embryo score: prediction of pregnancy outcome

PurposeTo compare pregnancy and implantation rates when embryos are selected based on a single Day 3 (D 3) morphology score vs. a GES score plus sHLA-G expression.MethodsA prospective randomized study (n = 214) undergoing fresh ICSI cycles. Embryos were selected for transfer based on either Day 3 morphology score (Group A) or GES-scoring plus sHLA-G expression (Group B).ResultsClinical [35/107 (33%) vs. 52/107 (49%)] and ongoing pregnancy [20/107 (19%) vs. 52/107 (49%)] rates were significantly different between Group A and Group B (p < 0.05). Implantation rates were not significantly different between Group A [52/353 (15%)] and Group B [73/417 (18%)] (p < 0.05). The number of pregnancies lost during the first trimester was nearly 12 times higher in Group A [25/52 (48%)].ConclusionThe miscarriage rate was significantly lower in Group B than Group A and the pregnancy results were superior when embryos were selected based on GES plus sHLA-G expression.