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Biomedical subjects

J P Balmaceda

Publications and source records attributed to J P Balmaceda.

At least 19 recordsLinked to original sources

Multiple gestation as a marker of reproductive efficacy: learning from assisted reproductive technologies.

This study postulates that apart from the number of embryos transferred, women with multiple gestation represent a subgroup of highly fertile individuals, whose embryos implant with higher efficiency than women with single gestation. Furthermore, each embryo generated from these women has a higher chance of reaching full term. The objective of this study was to compare implantation rate with the outcome of pregnancy (up to week 20) in multiple gestations following assisted reproductive techniques. The study group comprised 162 women with multiple gestation after assisted reproduction, followed prospectively with at least three ultrasound examinations performed between weeks 5 and 20 after the last menstrual period. Control group A comprised 344 fertile women with spontaneous single pregnancy followed with transvaginal ultrasound. Control group B consisted of 317 infertile women conceiving with single gestation after assisted reproduction and followed prospectively as in the study group. Embryo implantation rate and spontaneous embryo/fetal reduction, either partial or total (abortion), were registered in each case. Overall implantation in women with multiple gestation was higher (54.6%) than in the corresponding controls (25.6%). Furthermore, spontaneous embryo/fetus reduction was similar in the study cases and in fertile women (12.6 and 10.8% respectively) and significantly smaller than in the control group B (20.8%). Women with high reproductive efficacy exposed to assisted reproductive techniques generate cohorts of good quality embryos, with a high chance of implantation and of reaching birth.

Abortion, Spontaneous↗

Rare association of ovarian implantation site for patients with heterotopic and with primary ectopic pregnancies after ICSI and blastocyst transfer.

Two cases of patients with ruptured ovarian pregnancies (P1 = ovarian heterotopic and P2 = primary ovarian ectopic) after intracytoplasmic sperm injection and blastocyst transfer are presented. Laparoscopy was performed on day 40 and day 27 after transfer in cases P1 and P2 respectively. In both cases the ectopic pregnancies were located on the left ovary and were successfully removed by laparoscopy preserving the ovaries. In case P1 the intrauterine pregnancy was not affected. A healthy boy was born after 37 weeks of pregnancy. In this way, potential fertility of the patients and the intrauterine pregnancy were maintained. These cases occurred during a series of blastocyst transfers in which 129 pregnancies were obtained. There were no cases of ovarian ectopic/heterotopic pregnancies from January 1996 to September 1999 in 814 pregnancies obtained from day 2 or day 3 embryo transfers. Because the ovarian ectopic pregnancies occurred in patients with day 5 embryo transfer who otherwise did not have any predisposing factors for ectopic pregnancy, it is advisable to conduct a large scale analysis of future data about the possible association between blastocyst-stage embryo transfer and the somewhat higher risk of unexpected complications of clinical outcome.

Adult↗

Monozygotic twins and transfer at the blastocyst stage after ICSI.

The incidence of monozygotic twinning (MZT) is higher in pregnancies conceived after assisted reproduction than after natural conception. Alterations, produced by ovarian stimulation, in-vitro culture conditions and specifically alterations of zona pellucida are mentioned as possible causes of this phenomenon. A retrospective review was performed of the incidence of MZT in pregnancies generated in our centre during the period of January 1996 to December 1999. This variable was compared in 129 gestations that resulted from blastocyst transfer (occurring from September 1998 to August 1999) with 814 pregnancies produced by transfers of 4- to 8-cell embryos. Follicular development was induced with human menopausal gonadotrophin and urinary FSH during 1996 and 1997 and with recombinant FSH during 1998 and 1999. Blastocysts were cultured in sequential media using S1 or G1 up to 72 h and S2 or G2 to day 5. Five of the 129 pregnancies generated by blastocyst transfers were complicated by MZT gestation (3.9%). In comparison, only six of 814 pregnancies occurred from 4- to 8-cell transfers (0.7%), a difference that is statistically significant (P< 0.001 with Yates correction). The results confirm an increase of MZT in pregnancies from intracytoplasmic sperm injection as compared to the natural incidence. Moreover, the frequency of MZT was significantly higher when transfers were performed at the blastocyst stage, suggesting that extended in-vitro culture of embryos may be associated with alterations of the zona pellucida and the hatching process.

Adult↗

Prospective randomized trial to evaluate the efficacy of a vaginal ring releasing progesterone for IVF and oocyte donation.

A polysyloxane vaginal ring containing 1g of natural progesterone was developed as luteal supplementation for women treated with IVF-embryo transfer and for agonadal women participating in an oocyte donation programme. The ring provides continuous release of progesterone (10-20 nmol/l) for 90 days. The efficacy of this form of progesterone supplementation was evaluated in two multicentre prospective randomized trials. IVF-embryo transfer trial: After oocyte aspiration, 505 women were randomly allocated to progesterone supplementation with vaginal ring or i.m. progesterone (50 mg/day). The clinical pregnancy rate was 36.6% in both groups. Implantation rate was 15.9% in the vaginal ring and 16.0% in i.m. progesterone. Oocyte donation trial: After endometrial proliferation with micronized oestradiol, 153 women were allocated to progesterone replacement with a vaginal ring or i.m. progesterone (100 mg/day). Clinical pregnancy rate was 39.8 and 28.6% respectively. Implantation rate was significantly higher with the vaginal ring compared with i.m. progesterone (19.9 and 11.6% respectively, P = 0.006). The vaginal ring is a novel development which provides continuous release of progesterone for 90 days. In IVF-embryo transfer, its effectiveness is similar to daily i.m. injections. In oocyte donation the ring provides a progestative milieu which improves the implantation rate and eliminates the discomfort of daily i.m. injections.

Adult↗

Changes in expression of adenyl cyclase activity in human endometrium during hormone replacement therapy and ovarian stimulation.

We have investigated membrane fractions prepared from human endometrium for activity of the signalling adenyl cyclase (AC). We characterized the AC guanine nucleotide-binding proteins (G proteins) and examined the changes in AC activity during evaluation cycles of oestrogen and progesterone replacement therapy as well during ovarian stimulation cycles. AC activity was determined by the conversion of substrate ATP into cyclic AMP under basal conditions and in the presence of guanine nucleotide or forskolin. G proteins were determined by Western Blot using specific polyclonal antibodies against Gsalpha, Gi1,2alpha and Gi3alpha. Our results indicate that endometrial AC was highly responsive to activation by both guanine nucleotide and forskolin and its rate of cyclic AMP production was highly pronounced. Mean activity reached 920 pmol/l/min/mg membrane protein in the presence of forskolin, a value approximately 5-fold higher than those detected in corpus luteum. Hormonal induction of AC activities increased Gsalpha protein, which couples with and stimulates the catalytic component of AC. We conclude that human endometrium is rich in AC and that enzyme activity is induced by oestrogen and progesterone treatment. These data strongly support the concept that the transmembrane signalling AC system and its messenger cyclic AMP are major regulators of endometrial function in the human.

Adenylyl Cyclases↗

Vaginal bleeding and early pregnancy outcome in an infertile population.

OBJECTIVE: Our purpose was to determine the prognostic value of vaginal bleeding in early pregnancy outcome as well as to analyze the role of cardiac activity in predicting pregnancy viability in the presence of vaginal bleeding. STUDY DESIGN: This was a cohort study of pregnancies obtained using either assisted reproductive technology (ART) or routine infertility treatment (RIT). Two hundred twenty-eight pregnant women were divided into two groups based on the presence or absence of vaginal bleeding. Successive measurements of beta-hCG levels were obtained every 2 days, starting on day 14 after ovulation or embryo transfer. All pregnancies underwent weekly transvaginal ultrasound (UTZ) examinations beginning on day 21. The occurrence of vaginal bleeding was monitored weekly. RESULTS: Seventy of the 228 patients (31%) had bleeding in early pregnancy, resulting in 31 (44%) pregnancy losses. Only 22 pregnancy losses (14%) were observed in 158 patients who did not have bleeding (P < 0.001). The abortion rate for the bleeding versus nonbleeding groups was 35 and 9%, respectively (P < 0.001). Vaginal bleeding was associated with a higher abortion rate in pregnancies following RIT than ART (51 vs 8%; P < 0.001). Fetal cardiac activity was noted by vaginal ultrasound in 189 patients. In this subpopulation, bleeding was also associated with a higher abortion rate than that in the nonbleeding group (17 vs 4%; P < 0.001). However this higher incidence was observed only in pregnancies following RIT, not ART (28 vs 5%; P < 0.001). CONCLUSIONS: Although bleeding significantly decreased the chance of a normal pregnancy outcome, more than 50% of the pregnancies did progress to term. The presence of cardiac activity in this population as a sign of fetal viability offered a better pregnancy prognosis. However, the predictive value of fetal cardiac activity was reduced in the presence of vaginal bleeding in an infertile population treated with RIT.

Abortion, Spontaneous↗

Enzymatic characterization of zona pellucida hardening in human eggs and embryos.

PURPOSE: To characterize possible hardening of the human zona pellucida (ZP) and evaluate the effect of culture duration, patient age, and ZP thickness, ZP of unfertilized eggs (experiment 1, n = 367; experiment 2, n = 174) and abnormal embryos (experiment 1, n = 52) were randomly designated for alpha-chymotrypsin treatment after 0, 24, 48, 72, 96, 120 h (experiment 1) and 48 h, 72 h, and 1 week (experiment 2) of in vitro culture in HTF medium supplemented with 0.5% human serum albumin. Mean ZP thickness was predetermined in experiment 2. METHODS: The dispersion of the ZP glycoproteins was assessed, and the duration of time for complete digestion was recorded as an index of ZP hardness. RESULTS: In experiment 1, enzyme digestion duration increased (P < 0.05) in the first 24 h in vitro from 18.0 +/- 2.0 to 34.6 +/- 2.5 min, and tended to decrease over the next 4 days in culture (25.2 +/- 1.3, 29.4 +/- 0.9, 27.3 +/- 0.6, 26.6 +/- 1.1, and 20.7 +/- 1.5 min on Day 2-6 ZP, respectively). Zona hardening of fertilized eggs was revealed by a longer (P < 0.01) digestion time (32.2 +/- 1.8 vs 25.8 +/- 0.6 min). CONCLUSIONS: There were significant patient-to-patient variation (16.4 +/- 0.7 to 39.6 +/- 2.2 min); however, age was not correlated to enzyme digestion duration. In experiment 2 we determined that ZP thickness (range 8.4-21.6 microns; mean 14.6 +/- 0.2 microns) was not correlated (r = 0.09) to the digestion interval (mean 24.3 +/- 0.8 min). Based on our enzymatic ZP digestion measurements, it is apparent that spontaneous zona hardening does occur within 24 h of in vitro culture, similar to levels achieved postfertilization. The data do not support, however, the concept that additional, abnormal hardening of the ZP occurs during extended culturing.

Adult↗

The use of progestins for programming assisted reproductive cycles and gonadotropin-releasing hormone agonist flare-up protocols in older patients.

OBJECTIVES: To determine if the use of norethisterone acetate (NET) in the previous cycle affects the ovarian response to GnRH agonist (GnRH-a) in flare-up protocols and controlled ovarian hyperstimulation in older patients. DESIGN: Retrospective analysis of the outcome of the assisted reproductive technology (ART) cycle. PATIENTS: Eighty women > 37 years old undergoing controlled ovarian hyperstimulation (COH) for a ART cycle (GIFT, IVF, zygote intrafallopian transfer). Forty received NET during the luteal phase of the previous cycle for programming the procedure and 40 did not receive NET (control group). Gonadotropin-releasing hormone agonist in follicular phase (flare-up) protocols were administered to all the patients. MAIN OUTCOME MEASURES: Cycle outcome: amount of gonadotropins used, oocyte production and quality, fertilization, and pregnancy rates. Estradiol, FSH, and LH levels the first 3 days of COH in eight patients. RESULTS: There were no differences between both groups in the cycle outcome. Estradiol levels during the first 3 days of COH were higher in the patients that did not receive NET in the previous cycle. Follicle-stimulating hormone and LH levels were similar in both groups. CONCLUSIONS: The administration of NET in the previous cycle in patients > 37 years old does not affect the ovarian response to the combination of follicular phase GnRH-a and gonadotropins for COH.

Adult↗

Outcome of triplet pregnancies after assisted reproductive techniques: how frequent are the vanishing embryos?

OBJECTIVE: To assess the incidence of spontaneous embryo reduction as well as the obstetric and neonatal outcome of triplet gestations after assisted reproductive techniques (ART). METHODS: We analyzed the spontaneous outcome of 38 pregnancies in which three gestational sacs were identified with vaginal ultrasound between 21 and 28 days after ART. Weekly follow-up visits were scheduled during the first trimester until referral to a high-risk obstetrician. After delivery, each patient was interviewed individually and, if necessary, the obstetrician was contacted. RESULTS: The triplets delivery rate was 47.4%, whereas 31.6% delivered twins, 18.4% delivered singletons, and only one patient miscarried all three cases (2.6%). Finding three fetal heart beats was associated with a triplet delivery rate of 69.2%, a twin incidence of 19.2%, and a singleton birth rate of 11.6%. Embryo resorptions were observed mainly during the first 7 weeks of gestation and did not occur beyond the 14th week. The mean gestational age at delivery and neonatal birth weight were significantly lower among triplets (32.8 weeks and 1,740 g versus 35.3 weeks and 2,352 g in twins and 39.1 weeks and 3,122 g for singletons). Triplets had a 100% prematurity and cesarean section rate compared with 67% and 75% in twins and 0% and 43% in singletons, respectively. Hospitalization at the Neonatal Intensive Care Unit was required in 83% of newborn triplets, 29% of twins, and 0% of singletons, with a mean stay of 34 and 21 days for triplets and twins, respectively. One stillbirth and no neonatal deaths were reported, with an overall perinatal mortality rate of 11.9 per 1,000. CONCLUSIONS: Spontaneously, approximately 50% of triplet pregnancies will experience at least one embryo resorption. The ongoing triplets demand a complex and more expensive perinatal management, a strong argument to consider limiting the number of oocytes-embryos transferred in ART.

Birth Weight↗

The abnormally large follicle during controlled ovarian hyperstimulation: management and outcome of the cycle.

OBJECTIVE: To investigate if the presence of an abnormally large follicle during controlled ovarian hyperstimulation (COH) under pituitary suppression has any effect on the outcome of the cycle. DESIGN: Prospective, observational. SETTING: The reproductive endocrinology unit of a university hospital. PATIENTS: One hundred fifty patients undergoing COH for assisted reproductive techniques during a 6-month period (August 1990 to January 1991). INTERVENTIONS: Transvaginal follicular aspiration and IVF-uterine ET. RESULTS: A total of 19 cycles had abnormally large follicles identified on day 8 of the stimulation cycle after normal baseline ultrasound. Gonadotropins were continued and hCG injection was indicated when two or more follicles of the main cohort achieved a diameter of 20 to 22 mm. Twenty preovulatory oocytes were retrieved from 22 large follicles. Two were transferred for GIFT and 18 were inseminated in vitro, resulting in a 72.0% fertilization rate. The mean number of oocytes retrieved per patient was 10.9, 71.4% of which were mature with a fertilization rate of 67.7%. All these figures were comparable with the results obtained in the 131 patients of the control group undergoing IVF. No evidence of premature luteinization was observed in the study group, based on plasma P levels (x 0.83 ng/mL [conversion factor to SI unit, 3.180], range 0.31 to 1.40 ng/mL). The clinical pregnancy rate for the group with abnormally large follicles did not differ from the control group (27.8% versus 28.2%, respectively). CONCLUSIONS: The presence of an abnormally large follicle during COH under pituitary suppression does not affect the outcome of the cycle. Moreover, under these conditions, continuous gonadotropin stimulation of a follicle to diameters considerably larger than the standard ones does not have a detrimental effect on the oocyte contained in it, suggesting that oocyte aging is an independent process from follicular growth once LH surge is prevented.

Adult↗

Enzymatic amplification of specific deoxyribonucleic acid sequences from single cells: evaluation of a simplified and rapid method for use in preimplantation genetic diagnosis.

OBJECTIVE: To develop a simplified polymerase chain reaction (PCR) protocol on single cells for the purpose of preimplantation genetic diagnosis. Also to evaluate a new thermal cycler, RoboCycler 40 (Stratagene, La Jolla, CA), for reducing the time to complete PCR amplification. DESIGN: PCR amplification without DNA purification or reamplification of a 149 base pair (bp) segment of the human Y chromosome was used as a model. The assay was tested in human fetal cells, single lymphocytes and single human blastomeres. RESULTS: Amplification of the 149 bp segment using fetal cells was 100% correct. Results on single lymphocytes were concordant in all but one of the 15 male cases. However, 2 of the 25 female cases were identified as male suggesting the occurrence of DNA contamination. Analysis of 61 blastomeres were concordant in 57 cases (93%); results for male blastomeres showed 12% of false negatives. No false positives were detected for female cells. Amplification using the simplified PCR protocol in combination with the RoboCycler was completed in 2 hours. CONCLUSION: These data show that this PCR assay performed directly, without DNA extraction or purification and without re-amplification is a practical and effective approach for amplification of specific DNA sequences in single cells. Furthermore, the simplified PCR protocol significantly reduced the time to complete DNA amplification. The reduced time is expected to facilitate the management of a routine program for preimplantation genetic diagnosis.

Base Sequence↗

Successful fertilization, pregnancy, and birth using epididymal sperm frozen 24 hours after conventional oocyte insemination.

OBJECTIVE: To assess if epididymal sperm cryopreserved 24 hours after exposure to oocytes in conventional IVF can be successfully used for intracytoplasmic sperm injection (ICSI) in a subsequent cycle. DESIGN: Case report. SETTING: University of California, Irvine, Center for Reproductive Health. PATIENTS: Two men with obstructive azoospermia requiring microsurgical epididymal sperm aspiration, IVF, and ICSI. INTERVENTIONS: Freezing of epididymal sperm 24 hours after egg exposure in conventional IVF and subsequent use for assisted fertilization in a new cycle. MAIN OUTCOME MEASURE: Frozen-thawed epididymal sperm survivability and maintenance of fertilization and pregnancy capacity. RESULTS: At the time of sperm aspiration procedure (cycle I) a total of 30 oocytes were available for insemination. Of these, 15 were used for conventional IVF resulting in 2 embryos (13%) and 15 were used for ICSI, resulting in 3 embryos (20%). Sperm was cryopreserved 24 hours after conventional IVF and thawed 6 months later in a new cycle. Upon thawing, sperm were still found to be motile and at this time (cycle II) only assisted fertilization was used. Of 27 oocytes injected, 12 (44%) produced normal, cleaving embryos. One singleton pregnancy with the birth of a healthy infant girl was achieved after the tubal transfer of 5 embryos. CONCLUSION: The birth of a normal, healthy infant girl with epididymal sperm frozen 24 hours after exposure to oocytes in conventional IVF emphasizes the value of freezing any aliquot of epididymal sperm, even if the motility is very low, to avoid additional surgery in the male. From a basic science standpoint, this observation may renew interest in the study of sperm cryopreservation after occurrence of acrosome reaction and hyperactivation.

Cryopreservation↗

Successful pregnancy outcome after cryopreservation of all fresh embryos with subsequent transfer into an unstimulated cycle.

OBJECTIVE: To assess the pregnancy outcome of freezing and storing all fresh embryos produced in a stimulated IVF cycle and replacing them in a subsequent nongonadotropin-stimulated cycle. DESIGN: Retrospective study. SETTING: University-associated assisted reproductive technology program. PATIENTS: We studied 36 patients (age range 23 to 44 years) who underwent cryopreservation of all fresh embryos in a controlled ovarian hyperstimulation (COH) cycle because of either the risk of severe ovarian hyperstimulation (24 patients, group 1) or the presence of an endometrial lining < 8 mm in thickness (12 patients, group 2). Five hundred fifty-five embryos were generated for replacement in 63 cycles. All embryos were cryopreserved in 1.5 M propanediol at the pronuclear or two-cell stage, and 264 embryos subsequently were transferred into a hormone replacement cycle (70%) or natural ovulatory cycle (30%). The average number of embryos transferred per patient was 4.2. RESULTS: Twenty-one clinical pregnancies were achieved, giving a pregnancy rate (PR) of 58.3% per patient (33.3% per cycle). The live birth rate was 50% per patient (28.6% per cycle). The implantation rate was 9.1%. Groups 1 and 2 had a similar PR per patient (58.3%). With 208 cryopreserved embryos remaining and considering the 33.3% PR per cycle, we expect the overall extrapolated PR to be 63.9%. CONCLUSIONS: This is the first series showing that freezing and storing all fresh embryos produced in a stimulated IVF cycle and replacing them in a subsequent nongonadotropin-stimulated cycle results in successful PRs. These results underlie the importance of a successful cryopreservation program in IVF and could be a possible approach to overcoming the alleged adverse effects of COH on the endometrium, thereby improving the chances of pregnancy when numerous embryos are obtained simultaneously.

Adult↗

Use of epididymal sperm for assisted reproduction in men with acquired, irreparable obstructive azoospermia.

Microsurgical epididymal sperm aspiration (MESA) and in vitro fertilization (IVF) is primarily offered to men with congenital absence of the vas deferens (CAVD). However, the IVF capacity of these epididymal sperm is low ( < 15%) and unpredictable. In this study, IVF and intracytoplasmic sperm injection (ICSI) results in patients with non-congenital, irreparable obstructive azoospermia were analysed. Thirty-three patients were evaluated for a total of 37 cycles of MESA and IVF. Most had obstruction secondary to failed vasectomy reversal and to epididymal blockage. The overall fertilization rate was 30% with regular IVF and 26% with ICSI, and six clinical pregnancies were obtained. Both rates are significantly higher than the IVF rate previously reported with sperm from men with CAVD (13%, P < 0.00001). In men with non-congenital obstructive azoospermia, a significant difference was found in the average sperm count (56.9 x 10(6) v. 12.3 x 10(6), P < 0.04) and total motile count (16.6 x 10(6) v. 1.6 x 10(6), P < 0.01) respectively for patients who achieved IVF and those who did not. It is concluded that (a) the real IVF capacity of human epididymal sperm is 30%, or 42%, if calculated only for patients who achieved fertilization, (b) this higher rate is an indirect support of the hypothesis that sperm from men with CAVD have intrinsic biochemical defects, related to cystic fibrosis mutations, responsible for their low and unpredictable IVF rate, and (c) MESA and IVF can be offered at the same time or as an alternative to patients requesting vasectomy reversal.

Adult↗

Developmental competence of mouse embryos following zona drilling using a non-contact holmium:yttrium scandian gallium garnet (Ho:YSGG) laser system.

The purpose of this study was to assess the efficacy of the holmium:yttrium scandian gallium garnet (Ho:YSGG) laser, operating in a pipette-free, non-contact mode, to assist hatching and sustain normal embryonic development. Two-cell mouse embryos were recovered and assigned to laser-assisted hatching (LAH) treatment or control human tubal fluid (HTF) culture with or without serum (HTF-s, HTF-o) or with late serum supplementation (HTF-o/s). The basic experimental apparatus for LAH consisted of a stationary 2.1 microns Ho:YSGG laser beam directed through a mechanical shutter into an input port of a Zeiss Axiomat inverted microscope. Fewer (P < 0.05) embryos developed to the blastocyst stage in the HTF-s group (81%) than in the LAH (90%), HTF-o (94%) and HTF-o/s (92%) groups. The level of hatching was significantly increased (P < 0.01) after the LAH treatment (57%) compared to HTF-o/s (32%), HTF-s (18%) or HTF-o (5%). Implantation rates were not significantly impaired following the LAH treatment (21%). These data demonstrate that LAH using the Ho:YSGG laser is a simple, accurate and effective procedure for assisted hatching.

Animals↗

Physiological characterization of blastocyst hatching mechanisms by use of a mouse antihatching model.

OBJECTIVES: To use the protein-free medium blastocyst antihatching model to characterize physiological events that mediate hatching. DESIGN: In a series of four prospective experiments, our aims were to [1] test the efficacy of the antihatching model and assisted hatching; [2] exam the influence of initial in vivo developmental stage and late serum supplementation on hatching inhibition; [3] discount the role of zona hardness and physical expansion directly affecting hatching; and [4] provide evidence that the trophectoderm is directly responsible for secreting a zona lysin. SETTING: University-based research laboratory. RESULTS: Culturing two- to eight-cell mouse embryos in serum-free human tubal fluid (HTF) medium significantly reduced hatching levels to < or = 2%, however, hatching increased to 10.7% when initially culturing morula-stage embryos. Hatching was effectively rescued to control levels when embryos were placed in HTF with serum at the early blastocyst stage. There was no difference in blastocyst total cell numbers or zona pellucida digestion intervals between culture treatments. Finally, we showed that trophectodermal vesicles, devoid of inner cell mass, are capable of hatching under control conditions. CONCLUSIONS: The primary mechanism of blastocyst hatching is not physical expansion and abnormal zona hardness is not responsible for hatching inhibition. Certain extracellular precursors found in serum (e.g., amino acids) are required in culture medium upon cellular determination of trophectoderm (i.e., morula to blastocyst stage) to facilitate the intrinsic secretion of an undefined hatching factor.

Animals↗

Hysteroscopy and assisted reproductive technology.

Hysteroscopy is an excellent additional instrument for evaluating the uterine characteristics in infertile women. This article reviews the two main indications for hysteroscopy in infertile patients who are candidates for assisted reproductive techniques: (1) to evaluate the cervix and uterine cavity and (2) rule out any pathology or lesions that could have been missed by hysterosalpingography. Hysteroscopy has been proposed as an alternative method to traditional transabdominal transfer of gamete or embryo to the tube.

Cervix Uteri↗

Prospective randomized comparison of human chorionic gonadotropin versus intramuscular progesterone for luteal-phase support in assisted reproduction.

OBJECTIVE: The purpose of the study was to determine the impact of two forms of luteal-phase supplementation, human chorionic gonadotropin (hCG) and progesterone (P), during gonadotropin releasing hormone agonist (GnRh-a)/controlled ovarian hyperstimulation (COH) cycles. DESIGN AND PATIENTS: The study was a prospective, randomized evaluation of 77 patients. Group 1 patients (n = 38) received 2000 IU of hCG, injected subcutaneously, on days 3, 6, 9, and 12 after transvaginal aspiration of the oocytes (TVA = day 0). Group 2 patients (n = 39) received 50-mg daily injections of intramuscular (i.m.) P from days 2 to 14 after TVA. Blood tests were performed on days 0, 5, 8, and 12 after TVA. SETTING: The in vitro fertilization program of a tertiary care institution was the study setting. MAIN OUTCOME MEASURES: The main outcome measures were (1) pregnancy and implantation rates; (2) serum estradiol (E), P, and hCG levels; and (3) occurrence of side effects. RESULTS: Clinical pregnancy and implantation rates in group 1 versus group 2 were similar (36.7 vs 35.3 and 12 vs 14%, respectively). Regardless of pregnancy occurrence, on days 8 and 12 after TVA, serum E and P levels were higher in group 1 than group 2 but the resulting E/P ratios were similar. Five of 38 patients (group 1) developed moderate to severe ovarian hyperstimulation syndrome (OHSS) right after the first or second supplementary hCG injection. In these patients, the mean serum E level on the day of hCG trigger injection was about 3250 pg/ml and the number of follicles was between 9 and 17. In 6 of 39 patients (group 2) allergic reactions were observed at the P injection sites. CONCLUSIONS: Based on our data, hCG administration as a form of luteal supplementation did not translate, in comparison to P, into significant benefits for the patients. At the same time, it significantly increased the risk of ovarian hyperstimulation. We suggest that whenever, during COH cycles, serum E levels are over 2500 pg/ml and the number of follicles exceeds 10, luteal support with hCG should be excluded.

Adult↗