J.M. Knopman

Monozygotic twinning: an eight-year experience at a large IVF center

OBJECTIVE To characterize incidence, chorionicity, amnionicity, and pregnancy outcome for monozygotic twin pregnancy (MZT) after IVF. DESIGN Retrospective review. SETTING University-based fertility center. PATIENT(S) Autologous and oocyte donation IVF cycles eventuating in 4,976 clinical gestations from 2000 to 2007. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) MZT incidence, chorionicity, zygosity, pregnancy outcome. RESULT(S) Ninety-eight MZTs were diagnosed after first-trimester ultrasound evaluation (2% incidence). The incidence in cycles transfering autologous oocytes was 1.7% but was 3.3% with donor oocytes; however, women <35 years old using their own oocytes displayed a similar rate (3.1%) to women using donor oocytes. Eighty MZTs occurred after fresh day-5 transfer; only 14 followed fresh day-3 transfer (2.6% vs. 1.2%). The MZT incidence in day-3 transfers without hatching was not different from those with hatching (1.3% vs. 1.1%). In addition, MZT incidence did not differ significantly whether or not ICSI was performed (2.4% vs. 2.0%). Four MZTs occurred after frozen-thawed embryo transfer (0.8% incidence). Ninety-five percent of all placental arrangements were confirmed as monochorionic-diamniotic on obstetric ultrasounds. CONCLUSION(S) These findings confirm a higher incidence of MZT after IVF. Monochorionic-diamniotic implantations were increased, whereas monochorionic-monoamniotic were not. The MZT risk factors included young age and extended culture, but not zona penetration or cryopreservation.

Oocyte cryopreservation outcomes including pre-cryopreservation and post-thaw meiotic spindle evaluation following slow cooling and vitrification of human oocytes

OBJECTIVE To report our oocyte cryopreservation (OC) outcomes including meiotic spindle (MS) evaluation of metaphase II (MII) oocytes destined for OC and thaw. DESIGN Retrospective. SETTING University-based infertility center. PATIENT(S) Women attempting pregnancy using cryopreserved oocytes. INTERVENTION(S) OC, MS evaluation. MAIN OUTCOME MEASURE(S) Survival, two pronuclear (2PN) fertilization, achieving embryo quality suitable for transfer or refreezing, blastocyst formation. RESULT(S) Thirty-two OC-thaw cycles resulted in 20 pregnancies, 18 either ongoing or delivered. In 26 cycles, MS evaluation was performed: 262/303 (86%) thawed/recovered oocytes survived, 218/262 (83%) achieved 2PN fertilization, 133/218 (61%) became suitable for day-3 and 122/218 (56%) for day-5 transfer. In total, 58 embryos were transferred resulting in a 62% pregnancy and a 41% implantation rate. Of oocytes evaluated before cryopreservation, 247 (82%) were spindle-positive; 96% of these were also spindle-positive after thawing. Blastocyst formation and suitability for day-5 transfer was achieved more often if a post-thaw spindle was visualized. Of all slow-cooled and vitrified oocytes, a higher percentage of those slow-cooled achieved 2PN fertilization and usability. MS evaluation of oocytes cryopreserved by either method was associated with similar outcomes. CONCLUSION(S) OC outcomes are improving. An MS was almost always exhibited both before cryopreservation and after thawing, suggesting that, with appropriate technique, OC presents minimal harm to the MII oocyte. A meiotic spindle evaluation might help to further OC technology.

Women with cancer undergoing ART for fertility preservation : a cohort study of their response to exogenous gonadotropins

Cancer patients produce similar numbers of oocytes after ovarian hyperstimulation compared with age-matched infertile controls, suggesting that malignancy does not adversely affect ovarian response.

Surviving childhood and reproductive-age malignancy: effects on fertility and future parenthood

Annually, more than 50,000 cancer diagnoses are made in the USA in patients under the age of 35 years. Despite this staggering statistic, medical advancements have substantially improved survival rates. Thus, for both male and female patients with cancer, quality-of-life issues, such as fertility preservation and parenthood, have become an essential component of treatment. Unfortunately, many of the treatments to eradicate malignant processes can also compromise reproductive function. In these cases, fertility preservation should be discussed and initiated with early treatment planning, to allow the best chance for future parenthood, when appropriate. The effects of cancer and cancer treatments on fertility and future parenthood, including health risks for patients, their gametes, and offspring are discussed.

Fertility considerations in the management of gynecologic malignancies.

GOALS Gynecologic cancers represent a significant proportion of malignancies affecting women. Historically, cancer treatment focused primarily on eradicating disease, irrespective of the impact on fertility. The implementation of early detection protocols and advanced treatment regimens has resulted in improved prognosis for gynecologic cancer patients. With this improvement, more attention is now paid to quality-of-life issues. Fertility preservation (FP) has become an integral component in the selection and execution of gynecological cancer management. In this report we address gynecologic malignancies as they relate to future fertility potential. METHODS We review reproductive principles such as ovarian reserve, uterine function, cervical competence, and early obstetrical management, as well as available FP methods. In addition, we discuss the potential damage that cancer and cancer treatments can impart on the female reproductive system. We offer general recommendations regarding baseline screening tests useful in assessing the feasibility of FP. Lastly, cancer-specific FP methods are presented. RESULTS Oocyte quantity and quality naturally decline with advancing age. In most patients, the slope of decline steepens significantly after the age of 35. Reliable ovarian reserve measures exist and should be utilized to assess and triage potential candidates for FP. Advancements in FP, particularly in oocyte cryopreservation (OC), have improved the success rates associated with the techniques available to cancer patients. Currently, where successfully available, OC appears to be the preferred method for single women diagnosed with a gynecologic malignancy as it affords reproductive autonomy, whereas embryo cryopreservation using a donor gamete remains an alternative. CONCLUSIONS In gynecologic oncology, effective treatments to achieve cancer survival can compromise the ability to subsequently conceive and/or carry a child. Therefore, as the field of oncofertility continues to expand, a discussion regarding FP should be initiated when tailoring a cancer treatment protocol.

Cryopreserved oocytes can serve as the treatment for secondary infertility: a novel model for egg donation.

OBJECTIVE To report the use of previously cryopreserved oocytes for the treatment of secondary infertility. DESIGN Case report. SETTING University-based IVF program. PATIENT(S) A 41-year-old woman with 18 months of secondary infertility and a previous history (age 38) of elective oocyte cryopreservation. INTERVENTION(S) Previously cryopreserved oocytes. MAIN OUTCOME MEASURE(S) Fertilization, embryo development, pregnancy, and outcome. RESULT(S) The patient achieved pregnancy and delivery following thaw of oocytes electively cryopreserved 39 months before use. Before thawing the oocyte, the patient attempted pregnancy naturally for 12 months, followed by two unsuccessful clomiphene citrate ovulation induction cycles with intrauterine insemination and one fresh IVF cycle resulting in a chromosomally abnormal twin gestation that aborted. CONCLUSION(S) Although oocyte cryopreservation is still labeled an experimental procedure, this case demonstrates that oocyte cryopreservation used for electively deferred reproduction can subsequently serve in the treatment for secondary infertility when the patient becomes her own oocyte donor.

Fate of cryopreserved donor embryos.

OBJECTIVE To review a centers experience with cryopreserved embryos generated from donor eggs and to analyze their long-term disposition. DESIGN Retrospective analysis of donor egg cycles with cryopreserved embryos. SETTING University-based IVF program. PATIENT(S) Eight hundred twenty-nine women undergoing oocyte donation. INTERVENTION(S) N/A. MAIN OUTCOME MEASURE(S) Factors affecting the decision regarding disposition of donor frozen embryo transfer (dFET) and the association between fresh and dFET cycles. RESULT(S) From January 2000 to December 2004, donor egg recipients underwent 829 fresh embryo transfer cycles that resulted in a 54% live birth rate. Of the 444 recipients who delivered, 177 (40%) also cryopreserved embryos at transfer; however, only 37 (21%) returned for a dFET by August 2009 and only 18 women had children from fresh and frozen transfers. In contrast, 128 of the 385 recipients who failed the fresh transfer (33%) cryopreserved embryos and 111 (87%) returned for a dFET. Of these, 44 had children from the dFET. Frozen cycle success rates between these recipient groups did not depend on fresh cycle outcome or prior parity. CONCLUSION(S) Donor oocyte recipients often initiate treatment with a desire to cryopreserve embryos for future use and family expansion. However, our data demonstrates that most recipients with a child from the fresh transfer do not return to use their cryopreserved embryos. Although fresh transfer success correlated with embryo disposition, it did not correlate with the outcome of thawed embryo transfer.

Mitigating the Risk: The Role of Ovarian Transposition and Medical Suppression

While much of the focus within oncofertility is on fertility preservation options that are performed prior to initiation of cancer treatment, there are two fertility preservation measures that can be performed during treatment in an attempt to reduce the gonadotoxicity of radiation therapy and chemotherapy. For women who must undergo pelvic radiation therapy, ovarian transposition, also called oophoropexy, can be used to surgically reposition the ovaries away from the planned field of radiation. Medical suppression of the ovary with gonadotropin-releasing hormone (GnRH) agonists, given concurrent with chemotherapy, is thought to have a protective effect on the ovary and follicles, though the mechanisms and clinical efficacy of this approach remain unproven and controversial. This chapter describes each of these procedures and reviews the clinical data on their use in patients wishing to preserve their fertility.

What Is the Outcome and Fate of Frozen Supernumerary Embryos Resulting from Egg Donation

Cryopreservation of supernumerary embryos affords patients the potential opportunity to achieve multiple pregnancies from a single fresh IVF cycle or to at least have a second chance at success if the first attempt failed. In addition, the availability of frozen embryos reduces overall patient cost and increases the cumulative odds of pregnancy per case. Embryo cryopreservation is of particular importance in oocyte donation cycles because the number of embryos available frequently exceeds that which is acceptable (or desirable) for embryo transfer. Furthermore, limited resources specific to oocyte donation, including donor availability and cost, augment the appeal of cryopreservation. Despite the desire to cryopreserve supernumerary embryos at the time of the fresh donor oocyte transfer, more often than not, patients do not return to use their surplus embryos. Analysts estimate that as of 2003, over 400,000 embryos from all sources remained in storage facilities in the United States. As the number of IVF procedures has only grown over the past decade, we speculate that this number has nearly doubled.