Richard H. Reindollar

Congenital absence of the uterus and vagina is not commonly transmitted as a dominant genetic trait: Outcomes of surrogate pregnancies

OBJECTIVEnTo determine the inheritance pattern of congenital absence of the uterus and vagina in affected women undergoing surrogacy IVF with this disorder.nnnDESIGNnRetrospective study.nnnSETTINGnA hospital-based reproductive endocrinology and infertility center.nnnPATIENT(S)nWomen diagnosed with congenital absence of the uterus and vagina undergoing IVF with subsequent transfer of embryos to a surrogate uterus.nnnINTERVENTION(S)nQuestionnaires were sent to all infertility treatment centers performing surrogate procedures.nnnMAIN OUTCOME MEASURE(S)nNumber, gender, and frequency of congenital anomalies in progeny.nnnRESULT(S)nThirty-two of 53 surveyed programs responded (60%). One hundred sixty-two IVF cycles were performed, and 34 liveborn children were delivered (half female). No congenital anomalies were found, except for one male child with a middle ear defect and hearing loss.nnnCONCLUSION(S)nThese results strongly suggest that congenital absence of the uterus and vagina, if genetically transmitted, is not inherited commonly in a dominant fashion.

Administration of progesterone before oocyte retrieval negatively affects the implantation rate

OBJECTIVEnTo compare the efficacy of two clinically accepted methods of progesterone supplementation during IVF.nnnDESIGNnProspective randomized trial.nnnSETTINGnA university-based IVF program.nnnPATIENT(S)nThree hundred fourteen stimulated IVF cycles between January 1993 and October 1994.nnnINTERVENTION(S)nPatients were assigned to one of two luteal phase progesterone regimens by a random permuted block design. In protocol A, 12.5 mg of IM progesterone was given 12 hours before oocyte retrieval; in protocol B, 25 mg of IM progesterone was given on the day of oocyte retrieval.nnnMAIN OUTCOME MEASURE(S)nClinical pregnancy.nnnRESULT(S)nPatient demographic characteristics, including age, diagnosis, number of oocytes retrieved and fertilized, and number of embryos transferred, were not different between the two groups. There was no difference in the rate of cycle cancellation between the groups. One hundred forty ETs were performed in patients assigned to protocol A and 142 in patients assigned to protocol B. The clinical pregnancy rate in group A was 12.9% compared with 24.6% in group B.nnnCONCLUSION(S)nThe administration of progesterone before oocyte retrieval is associated with a lower pregnancy rate than the administration of progesterone after oocyte retrieval.

Role for anti-Müllerian hormone in congenital absence of the uterus and vagina.

Molecular genetic techniques were used to determine if mutations in the genes encoding anti-Müllerian hormone (AMH) (also known as Müllerian inhibiting substance (MIS)) and its receptor (AMHR) are commonly present in patients with congenital absence of the uterus and vagina (CAUV). Twenty-two CAUV patients and 96 control subjects from diverse ethnic groups were studied after obtaining informed consent. Genomic DNA samples prepared from leukocytes were digested separately with several different restriction enzymes, and the resultant fragments were analyzed for restriction fragment melting polymorphisms (RFMPs) by denaturing gradient gel electrophoresis (DGGE). Electrophoretic mobility of DNA fragments which were 200-700 base pairs in length was compared using polyacrylamide gels that included linear gradients of denaturing solvents designed to separate DNA fragments according to sequence-dependent variation in thermal stability. Two RFMPs were found in the AMH gene in both patients and normal control subjects. One RFMP in the AMHR gene was present at low frequencies in both patients and normal control subjects. No RFMPs specific to CAUV patients were found in either gene. Because no mutations or rare DNA sequence polymorphisms were detected in the AMH and the AMHR genes in this group of CAUV patients, it is unlikely that either gene commonly has an etiologic role in CAUV.

A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T)

OBJECTIVEnTo determine the optimal infertility therapy for women at the end of their reproductive potential.nnnDESIGNnRandomized clinical trial.nnnSETTINGnAcademic medical centers and private infertility center in a state with mandated insurance coverage.nnnPATIENT(S)nCouples with ≥ 6 months of unexplained infertility; female partner aged 38-42 years.nnnINTERVENTION(S)nRandomized to treatment with two cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant.nnnMAIN OUTCOME MEASURE(S)nProportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after two treatment cycles and at the end of treatment.nnnRESULT(S)nWe randomized 154 couples to receive CC/IUI (N = 51), FSH/IUI (N = 52), or immediate IVF (N = 51); 140 (90.9%) couples initiated treatment. The cumulative clinical pregnancy rates per couple after the first two cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatments, 110 (71.4%) of 154 couples had conceived a clinically recognized pregnancy, and 46.1% had delivered at least one live-born baby; 84.2% of all live-born infants resulting from treatment were achieved via IVF. There were 36% fewer treatment cycles in the IVF arm compared with either COH/IUI arm, and the couples conceived a pregnancy leading to a live birth after fewer treatment cycles.nnnCONCLUSION(S)nA randomized controlled trial in older women with unexplained infertility to compare treatment initiated with two cycles of controlled ovarian hyperstimulation/IUI versus immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group.nnnCLINICAL TRIAL REGISTRATION NUMBERnNCT00246506.

Ultrasound prediction of follicle volume: is the mean diameter reflective? *

OBJECTIVEnTo evaluate the relationship between 2 dimensional sonographic measurement of ovarian follicles and their actual volume.nnnDESIGNnProspective clinical study.nnnSETTINGnThe in vitro fertilization (IVF) program of a University based, tertiary care hospital.nnnPATIENTS AND INTERVENTIONSnSonographic categorization by shape, and measurement of 96 individual ovarian follicles immediately prior to aspiration for IVF. Each follicle was aspirated under direct ultrasound guidance and the volume recorded. The 96 follicles were visualized in a total of 14 patients from whom 2 to 27 oocytes were obtained.nnnMAIN OUTCOME MEASUREnTotal volume of each follicle.nnnRESULTSnRound and polygonal follicles exhibited a highly significant relationship between sonographically measured mean diameter and total follicle volume. The volume of follicles that were categorized as ellipsoid was not predicted by measurement of the longest diameter, shortest diameter or mean diameter.nnnCONCLUSIONnThe mean diameter of round and polygonal follicles accurately predicts total follicular volume. However, clinical decisions in ovulation induction should be modified when the follicle shape is predominantly ellipsoid because the traditionally held belief that the sonographic measurement of the follicular diameter correlates with the follicular volume does not apply in those circumstances.

Failed fertilization after intracytoplasmic sperm injection: the extent of paternal and maternal chromatin decondensation

OBJECTIVEnTo determine the extent of paternal and maternal chromatin decondensation in unfertilized eggs after intracytoplasmic sperm injection (ICSI).nnnDESIGNnEggs that failed to show two pronuclei (2-PN) 48 hours after ICSI were studied at two different time intervals: at ICSI program inception (group A) and after 8 months (group B).nnnPATIENT(S)nForty-nine patients undergoing IVF cycles.nnnMAIN OUTCOME MEASURE(S)nThe unfertilized eggs were studied by chromatin staining.nnnRESULT(S)nThe average fertilization rate from all ICSI cycles in these two groups was 45%. The fertilization rates in groups A and B were 35% and 59%, respectively. In group A, 65% of the unfertilized eggs were characterized by condensed sperm chromatin with 11% showing partial decondensation. In group B, only 28% of the unfertilized eggs demonstrated condensed sperm chromatin, whereas 45% were partially decondensed. In these two groups, no sperm chromatin was detected in 24% of the unfertilized eggs. The maternal chromatin remained at metaphase II in 84% of all unfertilized eggs analyzed.nnnCONCLUSION(S)nThese observations suggest that the technical problem of deposition of the sperm inside the egg is not the major cause of failure of fertilization rates in ICSI cycles. Rather, it is likely to be the failure to complete both the maternal and paternal chromatin transitions that occur with normal fertilization.

Aberrant estradiol flare despite gonadotropin-releasing hormone-agonist-induced suppression is associated with impaired implantation*

Our results confirm the previous report that rapid suppression by GnRH-a is favorable relative to delayed suppression (1). They further indicate that the pattern of E2 production during GnRH-a-induced ovarian suppression may be predictive of cycle outcome. We suggest that imperfect pituitary suppression of bioactive LH as indicated by an aberrant rise in E2 during GnRH-a down-regulation may compromise oocyte quality and ultimately impair implantation. Further study of follicular phase E2 response to GnRH-a suppression may provide a prognostic marker for implantation.

Canalization failure of the müllerian tract

A patient is described with canalization failure of the müllerian system. This patient presented with primary amenorrhea and absence of the vagina. At the time of laparotomy, a uterus of normal size and shape was found with two small areas of canalization. This syndrome, associated with absence of the vagina, appears to result from a defect occurring later in development than does classical müllerian aplasia. Pathological examination of the patients uterus supports the tenant that canalization begins after fusion and at various places along the line of fusion.

Technical and physiological aspects associated with the lower fertilization following intra cytoplasmic sperm injection (ICSI) in human

The fertilization rates with ICSI range from 30% to 70% and suggest that, despite injecting sperm into mature oocytes, significant fertilization failure still occurs in humans. The objective of this study was to determine technical and physiological factors which may contribute to lower fertilization following ICSI. Eggs that failed to show two pronuclei (PN) 48 hours after ICSI were studied at two different time intervals: at ICSI program inception (group A) and after 8 months (group B). The eggs were analyzed by staining with DNA fluorochromes, Hoescht 33258 and DAPI. The extent of sperm head as well as maternal chromatin decondensation in unfertilized ICSI eggs was determined by high resolution fluorescence microscopy. The average fertilization rate (FR) from all ICSI cycles in these two groups was 45%. The FR in Groups A and B were 35% and 59%, respectively (P < 0.05). In Group A, 65% of the unfertilized eggs were characterized by condensed sperm chromatin with 11% showing partial decondensation. In Group B, only 28% of the unfertilized eggs demonstrated condensed sperm chromatin while 45% were partially decondensed. Sperm chromatin was not detected in 24% of all unfertilized eggs studied. The maternal chromatin remained at metaphase II in 84% of all unfertilized eggs analyzed. These observations suggest that the technical problem of deposition of the sperm inside the egg is not the major cause for failure of fertilization rates in ICSI cycles. The increased percentage of eggs undergoing sperm head decondensation may be related to subtle changes in technique as experience is gained over time. The failure of sperm head decondensation in some of the ICSI eggs may be associated with cytoplasmic immaturity but not nuclear maturity.

Embryo transfer techniques: an American Society for Reproductive Medicine survey of current Society for Assisted Reproductive Technology practices

OBJECTIVEnTo better understand practice patterns and opportunities for standardization of ET.nnnDESIGNnCross-sectional survey.nnnSETTINGnNot applicable.nnnPATIENT(S)nNot applicable.nnnINTERVENTION(S)nAn anonymous 82-question survey was emailed to the medical directors of 286 Society for Assisted Reproductive Technology member IVF practices. A follow-up survey composed of three questions specific to ET technique was emailed to the same medical directors. Descriptive statistics of the results were compiled.nnnMAIN OUTCOME MEASURE(S)nThe survey assessed policies, protocols, restrictions, and specifics pertinent to the technique of ET.nnnRESULT(S)nThere were 117 (41%) responses; 32% practice in academic settings and 68% in private practice. Responders were experienced clinicians, half of whom had performed <10 procedures during training. Ninety-eight percent of practices allowed all practitioners to perform ET; half did not follow a standardized ET technique. Multiple steps in the ET process were identified as highly conserved; others demonstrated discordance. ET technique is divided among [1] trial transfer followed immediately with ET (40%); [2] afterload transfer (30%); and [3] direct transfer without prior trial or afterload (27%). Embryos are discharged in the upper (66%) and middle thirds (29%) of the endometrial cavity and not closer than 1-1.5xa0cm from fundus (87%). Details of each step were reported and allowed the development of a common practice ET procedure.nnnCONCLUSION(S)nET training and practices vary widely. Improved training and standardization based on outcomes data and best practices are warranted. A common practice procedure is suggested for validation by a systematic literature review.