Aneuploidy in oocytes from women of advanced maternal age: analysis of the causal meiotic errors and impact on embryo development.

STUDY QUESTION: In oocytes of advanced maternal age (AMA) women, what are the mechanisms leading to aneuploidy and what is the association of aneuploidy with embryo development? SUMMARY ANSWER: Known chromosome segregation errors such as precocious separation of sister chromatids explained 90.4% of abnormal chromosome copy numbers in polar bodies (PBs), underlying impaired embryo development. WHAT IS KNOWN ALREADY: Meiotic chromosomal aneuploidies in oocytes correlate with AMA (>35 years) and can affect over half of oocytes in this age group. This underlies the rationale for PB biopsy as a form of early preimplantation genetic testing for aneuploidy (PGT-A), as performed in the 'ESHRE STudy into the Evaluation of oocyte Euploidy by Microarray analysis' (ESTEEM) randomized controlled trial (RCT). So far, chromosome analysis of oocytes and PBs has shown that precocious separation of sister chromatids (PSSC), Meiosis II (MII) non-disjunction (ND), and reverse segregation (RS) are the main mechanisms leading to aneuploidy in oocytes. STUDY DESIGN, SIZE, DURATION: Data were sourced from the ESTEEM study, a multicentre RCT from seven European centres to assess the clinical utility of PGT-A on PBs using array comparative genomic hybridization (aCGH) in patients of AMA (36-40 years). This included data on the chromosome complement in PB pairs (PGT-A group), and on embryo morphology in a subset of embryos, up to Day 6 post-insemination, from both the intervention (PB biopsy and PGT-A) and control groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: ESTEEM recruited 396 AMA patients: 205 in the intervention group and 191 in the control group. Complete genetic data from 693 PB pairs were analysed. Additionally, the morphology from 1034 embryos generated from fertilized oocytes (two pronuclei) in the PB biopsy group and 1082 in the control group were used for statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 461/693 PB pairs showed abnormal segregation in 1162/10 810 chromosomes. The main observed abnormal segregations were compatible with PSSC in Meiosis I (MI) (n = 568/1162; 48.9%), ND of chromatids in MII or RS (n = 417/1162; 35.9%), and less frequently ND in MI (n = 65/1162; 5.6%). For 112 chromosomes (112/1162; 9.6%), we observed a chromosome copy number in the first PB (PB1) and second PB (PB2) that is not explained by any of the known mechanisms causing aneuploidy in oocytes. We observed that embryos in the PGT-A arm of the RCT did not have a significantly different morphology between 2 and 6 days post-insemination compared to the control group, indicating that PB biopsy did not affect embryo quality. Following age-adjusted multilevel mixed-effect ordinal logistic regression models performed for each embryo evaluation day, aneuploidy was associated with a decrease in embryo quality on Day 3 (adjusted odds ratio (aOR) 0.62, 95% CI 0.43-0.90), Day 4 (aOR 0.15, 95% CI 0.06-0.39), and Day 5 (aOR 0.28, 95% CI 0.14-0.58). LIMITATIONS, REASON FOR CAUTION: RS cannot be distinguished from normal segregation or MII ND using aCGH. The observed segregations were based on the detected copy number of PB1 and PB2 only and were not confirmed by the analysis of embryos. The embryo morphology assessment was static and single observer. WIDER IMPLICATIONS OF THE FINDINGS: Our finding of frequent unexplained chromosome copy numbers in PBs indicates that our knowledge of the mechanisms causing aneuploidy in oocytes is incomplete. It challenges the dogma that aneuploidy in oocytes is exclusively caused by mis-segregation of chromosomes during MI and MII. STUDY FUNDING/COMPETING INTEREST(S): Data were mined from a study funded by ESHRE. Illumina provided microarrays and other consumables necessary for aCGH testing of PBs. None of the authors have competing interests. TRIAL REGISTRATION NUMBER: Data were mined from the ESTEEM study (ClinicalTrials.gov Identifier NCT01532284).

Maternal and neonatal health outcomes following assisted reproduction.

This study assessed the risk for maternal complications in women and neonatal outcomes in children conceived following assisted reproductive treatment as compared with spontaneously conception and also separately evaluated conventional IVF and intracytoplasmic sperm injection (ICSI). The prospective cohort included 1161 women with singleton pregnancies: 561 who conceived following assisted reproduction (223 following IVF and 338 following ICSI) and 600 who conceived spontaneously. No differences were observed in pregnancy complications (including spontaneous abortion, pregnancy-induced hypertension, gestational diabetes and Caesarean delivery) except for significantly increased risk for excess vaginal bleeding in assisted reproduction pregnancies (21.4% versus 12.9%; OR 1.67, 95% CI 1.18-2.37), which was prominent in women who reported polycystic ovary syndrome. Neonates born following assisted reproduction had increased risk for prematurity (10.6% versus 5.3%; OR 1.72, 95% CI 1.04-2.87), and IVF, but not ICSI, was associated with significantly increased risk for prematurity (OR 2.36, 95% CI 1.28-4.37) and low birthweight (OR 1.89, 95% CI 1.03-3.46). In conclusion, this study observed only an increased risk for excess vaginal bleeding as a pregnancy-associated complication in singleton pregnancies following assisted compared with spontaneous conception. However, singleton neonates born following IVF, but not ICSI, were at increased risk for prematurity.

Effect of seminal plasma application to the vaginal vault in in vitro fertilization or intracytoplasmic sperm injection treatment cycles-a double-blind, placebo-controlled, randomized study.

PURPOSE: To study whether intravaginal application of seminal plasma after follicle aspiration has the potential to increase implantation and clinical pregnancy rates after IVF-ET. METHODS: We conducted a prospective, double-blind, placebo-controlled randomized study of 230 patients undergoing IVF-ET cycles. 500 µL of Fresh seminal plasma from the patient's partner or culture medium (placebo) were injected in the vaginal vault just after follicle aspiration. The main outcome measured was ongoing clinical-pregnancy rate. RESULTS: After ET cancellation in ten patients due to lack of fertilization or embryo cleavage, 220 embryo transfers (103 and 117 in the study and control groups) resulted in a clinical pregnancy rate of 36.9 % and 29.1 % for the study and control groups, corresponding to a relative increase of 26.8 %. After an early pregnancy loss of 13.1 % (5/38) and 23.5 % (8/34) in the study and control groups respectively an ongoing pregnancy rate of 32.0 % (33/103) and 22.2 % (26/117) was achieved corresponding to a relative increase of 44.1 %. Multivariate logistic regression analysis adjusted for study group, age, infertility, and cycle characteristics did not demonstrate any parameter that could predict occurrence of clinical pregnancy rates after IVF-ET. CONCLUSIONS: Patients who underwent SP intravaginal insemination after oocyte pick-up reached higher implantation and clinical pregnancy rates following ET compared to controls, although the difference did not reach statistical significance. More studies and variable methodologies may clarify the potential clinical effect of SP in improving live birth rates after ART.

Surrogate in vitro fertilization outcome in typical and atypical forms of Mayer-Rokitansky-Kuster-Hauser syndrome.

BACKGROUND: The genital malformations in Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) are frequently accompanied by associated malformations whose forms were recently classified as typical (isolated uterovaginal aplasia/hypoplasia) and atypical (the addition of malformations in the ovary or renal system). The aim of this study was to compare the surrogate IVF performance of women with typical and atypical forms including their chances of achieving pregnancy. METHODS: The follow-up data on a total of 102 cycles of surrogate IVF in 27 MRKH patients treated in our department between 2000 and 2010 were analysed. Twenty patients with the typical form who underwent 72 IVF cycles were compared with seven patients with the atypical form who underwent 30 IVF cycles. The various examined parameters of these intended mothers were age, hormonal profile during controlled ovarian hyperstimulation and laboratory outcome. RESULTS: The mean number of gonadotrophin ampoules needed for stimulation and treatment duration was significantly higher in the atypical form (3600 ± 1297IU for 13 ± 2.3 days versus 2975 ± 967 IU for 11.6 ± 1.6 days, P≤ 0.01). Serum estradiol and progesterone levels measured on the hCG administration day were similar. A significantly higher mean number of follicles 12.6 ± 6 versus 8.9 ± 5.4, P≤ 0.03, metaphase II (MII) oocytes 8.7 ± 5.1 versus 6.7 ± 4.8, P≤ 0.05, fertilizations 6 ± 3.6 versus 4.4 ± 3.3, P≤ 0.03 and cleaving embryos 5.7 ± 3.8 versus 4.1 ± 3.3, P≤ 0.01 were available in patients with the typical form compared with those with the atypical form, respectively. There was no significant difference in fertilization rate, cleavage rate or the mean number of transferred embryos. Embryo quality of the transferred ones and pregnancy rate per cycle were also similar between the two groups. CONCLUSIONS: Women with the typical form of MRKH needed fewer gonadotrophins and for a shorter duration for ovarian hyperstimulation. The mean number of follicles, oocytes, MII oocytes, fertilizations and cleaving embryos was higher among women with the typical form. Pregnancy rates were similar since the available number and quality of transferred embryos to the surrogate mother were not affected.

Presence of IL-18 in testicular tissue of fertile and infertile men.

Recently, IL-18 was identified in human testes. Moreover, an inverse correlation was found between the levels of IL-18 and the number and motility of spermatozoa. We examined the presence of IL-18 protein in normal and impaired spermatogenesis. Testicular tissue specimens were taken from 25 nonobstructive azoospermic patients undergoing testicular sperm extraction and from autopsies of three healthy controls. The presence of IL-18 in human testicular cells was examined by immunohistochemical staining of paraffin-embedded sections, using a specific antibody for human IL-18. In testicular tissue of healthy controls as well as in study cases, presence of IL-18 was identified in somatic, mitotic, meiotic and post-meiotic cells in correlation with their presence. In all patients, Leydig cells were less intensively stained. Mitotic cells were immunostained in the control group and less intensively in hypospermatogenesis and maturation arrest subgroups. Primary spermatocytes were in general most efficiently stained. The expression of IL-18 mRNA (as examined by real-time PCR analysis) showed significantly lower expression in testicular tissues with impaired spermatogenesis when compared to normal tissues. We report the first study demonstrating the presence of IL-18 in human testicular tissue at the protein level. The presence of this cytokine in somatic as well as in different types of germ cells may suggest its involvement in the regulation of the spermatogenic process and steroidogenesis under physiological and pathological conditions.

In vitro maturation of human germinal vesicle-stage oocytes: role of epidermal growth factor-like growth factors in the culture medium.

BACKGROUND: In vitro maturation (IVM) of oocytes is a promising technique to reduce the costs and avert the side effects of gonadotrophin stimulation for IVF. The pregnancy rates from oocytes matured in vitro are still lower than those of in vivo stimulation cycles, indicating that optimization of IVM remains a challenge. Recently, it was demonstrated that LH exerts its action on ovulation, at least in part, through stimulation of the production of the epidermal growth factor family members amphiregulin (Areg) and epiregulin (Ereg) in pre-ovulatory follicles, and they, in turn, serve as paracrine mediators of LH. We aimed to investigate the effect of supplementation of the medium with Areg and Ereg on the maturation rate of immature oocytes. METHODS: A total of 105 sibling human germinal vesicle (GV) oocytes obtained after gonadotrophin stimulation were cultured in a complex defined medium either with or without supplemented recombinant human Areg (75 ng/ml) and Ereg (75 ng/ml) for 24 h. RESULTS: Significantly more oocytes reached the metaphase II stage at 24 h in media supplemented with Areg and Ereg (75.5 versus 36.5%, P < 0.001). In vitro matured oocytes retrieved from the two subgroups had no statistically significant difference in fertilization and cleavage rates or morphology scores. Overall, a significantly higher number of Day 2 (52.8 versus 26.9% P < 0.01) and Day 3 (45.2 versus 23%, P < 0.05) embryos originated from GV oocytes cultured in the Areg- and Ereg-enriched medium. CONCLUSIONS: Supplementation of the maturation medium with Areg and Ereg improves the maturation of human GV oocytes in vitro.

Cumulus cell gene expression predicts better cleavage-stage embryo or blastocyst development and pregnancy for ICSI patients.

BACKGROUND: Cumulus cell (CC) gene expression is suggested as a non-invasive analysis method to predict oocyte competence. There are, however, important between-patient differences in CC gene expression. These can be compensated when expression results are combined with patient and cycle characteristics using a multiple regression analysis model. METHODS: From ICSI patients stimulated with GnRH antagonist and recombinant FSH (n= 25) or GnRH agonist and highly purified menotrophin (n= 20), CC were collected and oocytes were individually fertilized and cultured. CC were analyzed for the expression of Syndecan 4 (SDC4), Prostaglandin-endoperoxide synthase 2 (PTGS2), Versican (VCAN), Activated leukocyte cell adhesion molecule, Gremlin 1, transient receptor potential cation channel, subfamily M, member 7 (TRPM7), Calmodulin 2 and Inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) using quantitative PCR. Results were analyzed in relation to the stimulation protocol. Within-patient variation in gene expression was related to oocyte maturity and developmental potential. Models predictive for normal embryo or blastocyst development and pregnancy in single embryo transfer cycles were developed. RESULTS: Mature oocytes have higher PTGS2 and lower VCAN expression in their cumulus. All genes except VCAN had a positive correlation with good embryo or blastocyst morphology and were used to develop predictive models for embryo or blastocyst development (P< 0.01). Specific models were obtained for the two stimulation protocols. In both groups, better cleavage-stage embryo prediction relied on TRPM7 and ITPKA expression and pregnancy prediction relied on SDC4 and VCAN expression. In the current data set, the use of CC expression for pregnancy prediction resulted in a sensitivity of >70% and a specificity of >90%. CONCLUSIONS: Multivariable models based on CC gene expression can be used to predict embryo development and pregnancy.

EGF-like growth factors as LH mediators in the human corpus luteum.

BACKGROUND: This study aims to investigate the role of epidermal growth factor-like ligands, amphiregulin (Ar) and epiregulin (Ep), in regulation of apoptosis in luteinized human granulosa cells. METHODS: Luteinized human granulosa cells were obtained from women undergoing IVF treatment. Ar and Ep mRNA levels were measured by real-time RT-PCR. The rate of apoptosis was measured by TUNEL. Progesterone levels were measured using radioimmunoassay. Ar- and Ep-induced activation of signaling cascades and Ar protein levels were detected by western blotting. RESULTS: LH stimulation of luteinized human granulosa cells induced biosynthesis of Ar and Ep mRNA in a time-dependent manner. The blockade of MEK (by U0126) reduced the expression of LH-induced Ar and Ep biosynthesis. Incubation of the cells with Ar and Ep completely abolished the increase in apoptosis rate induced by serum starvation, and concomitantly caused a pronounced increase in progesterone production. Stimulation of the cells with Ar and Ep also activated the ERK and AKT signaling cascades. Finally, we demonstrated that the pro-survival effect of Ar and Ep is partially dependent on their ability to induce progesterone production. CONCLUSIONS: Ar and Ep serve as pro-survival LH mediators in the human corpus luteum.

Peritoneal macrophage depletion by liposomal bisphosphonate attenuates endometriosis in the rat model.

BACKGROUND: Activation of macrophages is central to the implantation of endometriosis (EM). We examined the hypothesis that macrophage depletion by intraperitoneal (IP) injection of liposomal alendronate (LA) could result in EM attenuation in a rat model, thus supporting the notion of the pivotal role of macrophages in EM pathology. METHODS: In this study, 90 rats were subjected to an EM model and were divided randomly into seven groups: five groups were treated by 4x once-weekly IP injections of LA (0.02, 0.1, 1, 5 or 10 mg/kg) and the other two groups received saline injections (control) or empty liposomes. Sham-operated rats also received empty liposomes. Depletion of circulating monocytes was determined by flow cytometry analyzes of blood specimens. Four weeks after the initial surgery, the number, size and weight of implants were recorded, adhesions were graded, macrophage infiltration was assessed and the peritoneal fluid was analyzed for monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor alpha (TNFalpha). RESULTS: Monocyte depletion following IP LA administration resulted in an inhibitory effect on the initiation and growth of EM implants, as expressed by implantation rate, adhesion scoring, implants' size and weight (>0.1 mg/kg LA, P < 0.05). Reduced numbers of infiltrating macrophages were observed in implants of the 1 mg/kg LA group. Peritoneal fluid MCP-1 levels were negatively correlated with LA dose (P < 0.001), whereas no significant correlation could be found for TNFalpha. CONCLUSIONS: Macrophage depletion using IP LA has been shown to effectively inhibit the initiation and growth of EM implants, in a rat EM model. The clear dose-response effect may be viewed as a confirmation of the validity of the concept and encourages further study.

The possible association between IVF and breast cancer incidence.

BACKGROUND: The possible association between ovulation-inducing drugs and breast cancer development has been debated. Our aim was to evaluate the incidence of breast cancer in a cohort of women exposed to in vitro fertilization (IVF). METHODS: A retrospective cohort analysis was performed by linkage of the computerized database of all women treated at the IVF Unit at Assaf Harofeh Medical Center between 1986 and 2003, and the Israeli National Cancer Registry. The standardized incidence ratio (SIR) was computed as the ratio between the observed number of breast cancer cases and the expected cases, adjusted for age and continent of birth, in the general population. Tumor characteristics of the IVF patients were studied by reviewing original medical records. RESULTS: 35 breast carcinomas were diagnosed among 3,375 IVF-treated women, compared to 24.8 cases expected (SIR = 1.4; 95% CI 0.98-1.96). Age >or=40 years at IVF treatment (SIR = 1.9; 95% CI 0.97-3.30), hormonal infertility (SIR = 3.1; 95% CI 0.99-7.22), and >or=4 IVF cycles (SIR = 2.0; 95% CI 1.15-3.27) were found to be risk factors to develop breast cancer compared to the general population. Multivariate analysis revealed that women who underwent >or=4 IVF cycles compared to those with one to three cycles were at risk to develop breast cancer, although not significantly (SIR = 1.9; 95% CI 0.95-3.81). Of IVF-treated women 85% had ER(+) tumors and 29% had positive family history. CONCLUSIONS: A possible association between IVF therapy and breast cancer development was demonstrated, especially in women >or=40 years of age. These preliminary findings need to be replicated in other cohort studies.

Controlled intravenous bicarbonate and fetal-maternal acid-base balance. I. The primipara.

The effects of a controlled sodium bicarbonate (SB) infusion on the acid-base balance of the primiparous mother and fetus at labor and delivery were evaluated. Two identical groups of primiparas with normal labor and delivery were studied. According to acid-base parameters observed in the mothers and fetuses of a control group, the pharmacologic dynamics, and the space of distribution of SB, 2 mEq/1 kg of total body weight were administered to the mothers of the study group, beginning at a cervical dilation of 6 cm until full dilation occurred. Highly significant changes in pH, base excess (BE), and plasma bicarbonate were observed in both the mothers and fetuses. In the latter, the significant changes appeared after a time lag of about 2 hours. No adverse effects in the mothers and fetuses were observed. The significant reduction of the relative fetal acidosis by the controlled SB infusion justifies further studies on the therapy potentials of this method in high-risk deliveries and during intrapartum fetal distress.

The value of simultaneous hysterectomy during Burch colposuspension for urinary stress incontinence.

The effect of concomitant hysterectomy during colposuspension on the cure rate of genuine stress incontinence was evaluated prospectively in 45 patients. Twenty-two women underwent a colposuspension only (no-hysterectomy group) and 23 had a concomitant abdominal hysterectomy and cul-de-sac obliteration (hysterectomy group). Twenty-five months postoperatively, no differences were found in the cure rate for urinary stress incontinence between the two groups (95.5 and 95.7% for the no-hysterectomy and the hysterectomy group, respectively). In the no-hysterectomy group, three patients (13.6%) had enterocele formation after surgery; this complication did not occur in any of the patients in the hysterectomy group.

The effect of total abdominal hysterectomy on bladder function in asymptomatic women.

The effect of total abdominal hysterectomy as treatment for benign conditions on the postoperative incidence of urinary symptoms and abnormal urodynamic findings was evaluated in 16 premenopausal women who lacked urinary symptoms preoperatively. The urodynamic evaluation was performed preoperatively, at 4 weeks, and again at 4 months after surgery. No clinical symptoms of frequency, nocturia, urgency, or urge or stress incontinence were found postoperatively. There were no significant differences from the preoperative values for cystometry, uroflometry, and urethral pressure profiles. Urinary dysfunction should not be a consequence of an uncomplicated total abdominal hysterectomy for benign conditions in women who were previously free of urinary symptoms.

Unexpected cardiac pathology in pregnant women treated with beta-adrenergic agents (ritodrine).

Premature uterine contractions were treated by intravenous beta-mimetics in 190 patients during a 2-year period. History and physical examination were directed toward identification of patients with cardiac problems. Unexpected cardiac pathology was discovered in 14 patients, all of whom exhibited severe and continuous nausea, retrosternal pain, or dyspnea during beta-mimetic administration. Treatment was immediately discontinued in the presence of S-T depression, supraventricular tachycardia, nonspecific T wave changes, and sinus tachycardia with right axis deviation. Further investigation revealed obstructive cardiac myopathy in one case and atrial septal defect in another. Such changes might be identified earlier by more extensive screening procedures (such as electrocardiogram) before drug administration. Administration of beta-mimetic agents may uncover previously unexpected cardiac pathology. Continuation of ritodrine in such cases is contraindicated and potentially hazardous.

Triplet and quadruplet pregnancies and management.

The rate of multiple pregnancies with more than 2 fetuses has significantly increased since the introduction of ovulation induction agents. From 1970 through 1978, there were 19 triplets and 6 quadruplets in the authors' department, incidences of 1:696 and 1:5370, respectively. Eighteen (72%) of the 25 multiple pregnancies followed treatment with ovulation induction agents and 7 were spontaneous. The diagnosis of more than 2 fetuses was made earlier in the induced than in the uninduced pregnancies. Management, initiated upon diagnosis, included bed rest, high-protein diet, beta-mimetic agents, progestins, dexamethasone late in the second trimester, and selective cerclage. The mean gestational age was 34 weeks in the triplets and 35 weeks in the quadruplets. Forty-four percent of the deliveries were by cesarean section and the remainder were by vaginal delivery. The mean weight of the neonates was 1807 g in the triplets and 1950 g in the quadruplets. The mean overall Apgar score was 8.16, and the perinatal mortality was 185 per 1000, corrected (more than 28 weeks) to 137 per 1000. The main neonatal complications resulted from prematurity, and maternal complications noted were postpartum hemorrhage necessitating hysterectomy in 2 patients. The preferable mode of delivery cannot be stated dogmatically. Fetal outcome was similar in vaginal and cesarean deliveries among the various gestational age groups.

Early, late, and sequential embryo transfer in in vitro fertilization program: a preliminary report.

The timing of ET was evaluated by transferring four embryos at 44 to 48 hours, 68 to 72 hours, or equally dividing and sequentially transferring at 44 to 48 and 68 to 72 hours after insemination. Fifty-one patients were randomly allocated to one of the above protocols. The mean number of blastomeres of embryos transferred at 68 to 72 hours after insemination was significantly (P less than 0.0001) higher than those transferred at 44 to 48 hours. The number of embryos with good morphology was similar in all study groups. The pregnancy rate was similar in the three protocol groups, 53% at 44 to 48 hours, 59% at 64 to 72 hours, and 47% by sequential transfer. There probably is no advantage in delaying the transfer or dividing the embryos into two sequential transfers. It seems that sequential transfer is not associated with any harmful effect.

Spermatic vein ligation in varicocele: prognosis and associated male and female infertility factors.

The fertility outcome of 129 spermatic vein ligations with good postoperative anatomic results is analyzed. For each couple, specific attention was also directed to other infertility factors. The study analyzes four groups: group I, 55 patients with varicocele only; group II, 16 patients with varicocele and prostatovesiculitis; group III, 16 patients with varicocele and a severe degree of testicular failure; and group IV, 42 patients with a varicocele only and associated female infertility factors. In each group, the pregnancy rate within 6 to 24 months after the operation was recorded. The control subjects were 36 patients with varicocele only who had declined or postponed intervention for 6 months. The best results were obtained in group I. Sperm motility improved following ligation and was associated with a greater percentage of pregnancies within a shorter period: 51% and 62% within 6 and 12 months, respectively, as compared with the control group (14% within 6 months). The prostatic disease required additional treatment for a longer period, but results similar to those of group I were eventually obtained (50% pregnancy rate). With testicular failure or female infertility factors, the prognosis worsened (31% overall pregnancy rate).

Successful pregnancy after 24 consecutive fetal losses: lessons learned from surrogacy.

OBJECTIVE: To offer surrogacy as a treatment option to patients in whom maternal rather than fetal factors are responsible for high-order unexplained habitual abortions. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 36-year-old woman with 24 consecutive abortions over 11 years. INTERVENTION(S): A regular IVF procedure in the aborting woman and transfer of two good-quality embryos to the surrogate mother, who had previously received hormones. MAIN OUTCOME MEASURE(S): Ovarian response, oocytes, fertilization, and embryo quality in the aborting patient. Endometrial thickness, implantation, pregnancy, and delivery in the surrogate mother. RESULT(S): Transfer of two embryos to the surrogate mother led to a clinical pregnancy, which was uneventful until term. Cesarean section was performed for breech presentation, with delivery of a healthy male. CONCLUSION(S): Surrogacy can be offered as a treatment option to patients in whom maternal rather than fetal factors are responsible for high-order unexplained habitual abortions.

Birth of a triplet after transfer of four frozen-thawed embryos.

This is apparently the first triplet pregnancy after four freeze-thawed embryos that terminated in a birth of three healthy infants, with relatively good birth weights and uneventful follow-up.

Outcome of assisted reproductive technology in women over the age of 41.

OBJECTIVE: To analyze the results of ongoing pregnancies and deliveries after assisted reproductive technology (ART) in women aged >/=41 years, stratified by year of age. DESIGN: Retrospective study. SETTING: University hospital, IVF unit. PATIENT(S): A total of 431 IVF and intracytoplasmic sperm injection (ICSI) cycles were initiated in women >/=41 years of age. INTERVENTION(S): Medical files of ART patients and pregnancy outcomes were reviewed. MAIN OUTCOME MEASURE(S): Oocytes retrieved, embryos developed, and clinical pregnancy and delivery rates. RESULT(S): Of the 431 started cycles, 376 (87%) reached the oocyte retrieval stage. The mean number of oocytes aspirated per patient was 5.4 +/- 0.9 and 6.7 +/- 1.2 in the IVF and ICSI cycles, respectively, and the number of embryos obtained was 2.3 +/- 1.3 and 2.8 +/- 1.6 in the IVF and ICSI cycles, respectively. The number of transferable embryos was 2.0 +/- 1.2 and 2.5 +/- 0.8. The pregnancy rate per oocyte pickup (OPU) was 12.4%; however, the delivery rate per OPU was 4.5%. The mean delivery rate per OPU among women aged 41-43 years was 2%-7%. There were no deliveries aged >/=44 years and no pregnancies at the age of 45 years. The pregnancy and delivery rates of the ICSI and IVF patients were similar after stratification by age. CONCLUSION(S): In our studies, ART performed with homologous oocytes, whether by IVF or ICSI, yielded no clinical pregnancies among women aged >/=45 years and no deliveries aged >/=44 years. The mean delivery rate per oocyte retrieval among women aged 41-43 years varied between 2% and 7%.