Recovery and processing of human embryos formed in vivo

Abstract

A kit having instructions for use for performing uterine lavage in a female patient includes a uterine lavage catheter configured for insertion into a woman's uterus to remove viable blastocysts from the uterus, and one or more first containers having a sufficient dosage amount of a GnRH antagonist to cause desynchronization of the endometrium of the patient prior to, during and/or following recovery of viable blastocysts from the uterus.

1 . (canceled) 
     
     
         2 . A kit having instructions for use for performing uterine lavage in a female patient, comprising:
 a uterine lavage catheter configured for insertion into a woman's uterus to remove blastocysts from the uterus; and   one or more first containers comprising a sufficient dosage amount of a GnRH antagonist to cause corpus luteum apoptosis leading to desynchronization of the endometrium of the patient prior to, during and/or following recovery of viable blastocysts from the uterus.   
     
     
         3 . The kit according to  claim 2 , wherein the GnRH antagonist is present in a pharmaceutically acceptable carrier in a dosage form for administration to a patient. 
     
     
         4 . The kit according to  claim 2 , wherein the GnRH antagonist is present in a pharmaceutically acceptable carrier at a dosage amount of about 0.10 to 400.0 mg. 
     
     
         5 . The kit according to  claim 2 , wherein the GnRH antagonist is present in a pharmaceutically acceptable carrier at a dosage amount of about 0.5 to 5.0 mg. 
     
     
         6 . The kit according to  claim 2 , wherein the GnRH antagonist is present in a pharmaceutically acceptable carrier at a dosage amount of about 0.25 to 3.0 mg. 
     
     
         7 . The kit according to  claim 2 , wherein the GnRH antagonist comprises at least one of Cetrotide, Ganirelix, Abarelix, Degarelix, or Elagolix. 
     
     
         8 . The kit according to  claim 7 , in which the GnRH antagonist comprises Cetrotide 3.0 mg. 
     
     
         9 . The kit according to  claim 2 , further comprising one or more second containers comprising a sufficient dosage amount of FSH and/or LH to cause superovulation, in vivo fertilization, and/or embryonic maturation. 
     
     
         10 . The kit according to  claim 9 , including instructions for use for administering the FSH and/or LH by self-injection. 
     
     
         11 . The kit according to  claim 10 , in which the dosage amount of FSH and/or LH is appropriate for induction of superovulation, in vivo fertilization, and embryonic maturation. 
     
     
         12 . The kit according to  claim 10 , including instructions for use for self-injecting the FSH and/or LH using 5 to 20 daily injections at ranges of 12.5 to 1200 mIU per day. 
     
     
         13 . The kit according to  claim 11 , in which the FSH and/or LH comprises at least one of injectable menotropins containing both FSH and LH; urofollitropins containing purified FSH; recombinant pure FSH; or single doses of recombinant long acting pure FSH. 
     
     
         14 . The kit according to  claim 9 , further comprising one or more third containers comprising a sufficient dosage amount of GnRH antagonists to prevent premature ovulation while stimulating the ovaries with FSH and/or LH. 
     
     
         15 . The kit according to  claim 14 , in which the GnRH antagonists comprise receptor blocker peptides. 
     
     
         16 . The kit according to  claim 15 , in which the GnRH antagonists comprise at least one of Cetrotide 0.25 to 3 mg, Ganirelix, Abarelix, Degarelix, or Elagolix. 
     
     
         17 . The kit according to  claim 9 , further comprising one or more third containers comprising a sufficient dosage amount of GnRH agonist to prevent premature ovulation while stimulating the ovaries with FSH and/or LH. 
     
     
         18 . The kit according to  claim 14 , further comprising instructions for use for administering a single or multiples doses of GnRH agonist subcutaneously or nasally to trigger superovulation. 
     
     
         19 . The kit according to  claim 18 , in which the GnRH agonist comprises at least one of Leuprorelin, Leuprolide acetate, nafarelin, naferilin acetate snuff, or Buserelin. 
     
     
         20 . The kit according to  claim 14 , comprising instructions for use for administering a single or multiple doses of urinary or recombinant hCG or LH surrogate subcutaneously, orally, intramuscularly, transdermally, vaginally, rectally, buccally, or nasally to trigger ovulation. 
     
     
         21 . The kit according to  claim 17 , comprising instructions for use for administering a single or multiple doses of urinary or recombinant hCG or LH surrogate subcutaneously, orally, intramuscularly, transdermally, vaginally, rectally, buccally, or nasally to trigger ovulation. 
     
     
         22 . The kit according to  claim 20 , in which the hCG or LH surrogate comprises at least one of Pregnyl, Novarel, or Ovidrel. 
     
     
         23 . The kit according to  claim 2 , further comprising a lavage controller for controlling the delivery of pressure and the application of vacuum to the lavage catheter. 
     
     
         24 . The kit according to  claim 23 , wherein said lavage catheter further includes an expandable member, said catheter including a shaft having a distal portion and said expandable member being disposed along said distal portion. 
     
     
         25 . The kit according to  claim 2 , further comprising a cell-culture container for collecting lavage fluid from the lavage catheter and which maintains blastocyst-safe O2/CO2 levels without the requirement of an incubator. 
     
     
         26 . The kit according to  claim 2 , further comprising instructions for use for administering the GnRH antagonist before the day or on the day on which the blastocysts are recovered and daily for up to 10 days or until the onset of menses following blastocyst recovery to induce corpus luteum apoptosis. 
     
     
         27 . A kit for uterine lavage comprising:
 a uterine lavage catheter configured for insertion into a woman's uterus to remove blastocysts from the uterus;   one or more first containers comprising a sufficient dosage amount of FSH and/or LH appropriate for induction of superovulation in a woman; and   one or more second containers comprising a sufficient dosage amount of a GnRH antagonist to cause corpus luteum apoptosis leading to desynchronization of the endometrium following superovulation.   
     
     
         28 . The kit according to  claim 27 , wherein the GnRH antagonist is present in a pharmaceutically acceptable carrier in a dosage form for administration to a patient. 
     
     
         29 . The kit according to  claim 27 , wherein the GnRH antagonist is present in a pharmaceutically acceptable carrier at a dosage amount of about 0.25 to 10.0 mg. 
     
     
         30 . The kit according to  claim 27 , wherein the GnRH antagonist is present in a pharmaceutically acceptable carrier at a dosage amount of about 0.5 to 5.0 mg. 
     
     
         31 . The kit according to  claim 27 , wherein the GnRH antagonist is present in a pharmaceutically acceptable carrier at a dosage amount of about 0.25 to 3.0 mg. 
     
     
         32 . The kit according to  claim 27 , wherein the GnRH antagonist comprises at least one of Cetrotide, Ganirelix, Abarelix, Cetrorelix, Degarelix, or Elagolix. 
     
     
         33 . The kit according to  claim 27 , in which the GnRh antagonist comprises Cetrotide 3.0 mg. 
     
     
         34 . The kit according to  claim 27 , including instructions for use for administering the FSH and/or LH by self-injection. 
     
     
         35 . The kit according to  claim 34 , including instructions for use for self-injecting the FSH and/or LH using 5 to 20 daily injections at ranges of 12.5 to 1200 mIU per day. 
     
     
         36 . The kit according to  claim 27 , in which the FSH and/or LH comprises at least one of injectable menotropins containing both FSH and LH; urofollitropins containing purified FSH given as; recombinant pure FSH; or single doses of recombinant long acting pure FSH. 
     
     
         37 . The kit according to  claim 27 , further comprising a lavage controller for controlling the delivery of pressure and the application of vacuum to the lavage catheter. 
     
     
         38 . The kit according to  claim 27 , further comprising a cell-culture container for collecting lavage fluid from the lavage catheter. 
     
     
         39 . The kit according to  claim 27 , further comprising instructions for use for administering the GnRH antagonist before the day or on the day on which the blastocysts are recovered and daily for up to ten days or until the onset of menses following blastocyst recovery to induce corpus luteum apoptosis. 
     
     
         40 . The kit according to  claim 27 , further comprising one or more third containers comprising a sufficient dosage amount of a GnRH antagonist to prevent premature ovulation while stimulating the ovaries with FSH and/or LH. 
     
     
         41 . A kit for uterine lavage comprising a uterine lavage catheter configured for insertion into a woman's uterus to remove viable blastocysts from the uterus; one or more first containers comprising a sufficient dosage amount of FSH appropriate for induction of superovulation; one or more second containers comprising a sufficient dosage amount of a GnRH antagonist to prevent premature ovulation while stimulating the ovaries with FSH and/or LH; and one or more third containers comprising a GnRH antagonist to be administered after superovulation. 
     
     
         42 . A composition suitable for administration to a human female patient after superovulation comprising a GnRH antagonist in a pharmaceutically acceptable carrier at a dosage amount of about 0.5 to 400 mg, sufficient to cause corpus luteum apoptosis leading to desynchronization of the endometrium prior to, during, or following recovery of blastocysts from the uterus of the patient. 
     
     
         43 . The composition according to  claim 42 , wherein the GnRH antagonist is present in the pharmaceutically acceptable carrier at a dosage amount of about 0.5 to 5.0 mg. 
     
     
         44 . The composition according to  claim 42 , wherein the GnRH antagonist is present in the pharmaceutically acceptable carrier at a dosage amount of about 0.5 to 3.0 mg. 
     
     
         45 . The composition according to  claim 42 , wherein the GnRH antagonist comprises at least one of Cetrotide, Ganirelix, Abarelix, Degarelix, or Elagolix. 
     
     
         46 . The composition according to  claim 42 , wherein the GnRH antagonist comprises Cetrotide 3.0 mg. 
     
     
         47 . A method of inducing corpus luteum apoptosis leading to desynchronization of the endometrium in a female patient in which same is desired prior to, during and/or following recovery of blastocysts from the uterus of the patient, comprising administering a GnRH antagonist to the patient in a sufficient dosage amount to cause said desynchronization. 
     
     
         48 . The method of  claim 47 , including administering the GnRH antagonist on the day in which the blastocysts are recovered. 
     
     
         49 . The method of  claim 48 , further comprising administering the GnRH antagonist daily for up to ten days or until the onset of menses following blastocyst recovery to induce corpus luteum apoptosis. 
     
     
         50 . The method of  claim 47 , wherein the GnRH antagonist is administered at a dosage amount of about 0.10 to 400.0 mg. 
     
     
         51 . The method of  claim 47 , wherein the GnRH antagonist is administered at a dosage amount of about 0.5 to 10.0 mg. 
     
     
         52 . The method of  claim 47 , wherein the GnRH antagonist is administered at a dosage amount of about 0.5 to 5.0 mg. 
     
     
         53 . The method of  claim 47 , wherein the GnRH antagonist is administered at a dosage amount of about 0.25 to 3.0 mg. 
     
     
         54 . The method of  claim 47 , wherein the GnRH antagonist comprises at least one of Cetrotide, Ganirelix, Abarelix, Degarelix, or Elagolix. 
     
     
         55 . The method of  claim 47 , wherein the GnRH antagonist comprises at Cetrotide 3.0 mg. 
     
     
         56 . The method of  claim 47 , further comprising administering a progesterone receptor antagonist to the patient. 
     
     
         57 . The method of  claim 56 , wherein the progesterone receptor antagonist comprises Mifepristone, at a dosage of about 600 mg, with or without Misoprostol at a dosage of about 400 μg to 800 μg. 
     
     
         58 . The method of  claim 56 , wherein the progesterone receptor antagonist comprises Onapristone at a dosage of between 100 to 200 mg. 
     
     
         59 . The method of  claim 56 , wherein the progesterone receptor antagonist comprises Ulipristal. 
     
     
         60 . The method of  claim 56 , wherein the progesterone receptor antagonist comprises Org31710 at a dosage of between 10 to 75 mg. 
     
     
         61 . A uterine lavage system comprising:
 a fluid delivery and collection device; and   a controller programmed to deliver lavage liquid to the uterus to assist with the recovery of blastocysts from the uterus at a flow of fluid supply that is configured to substantially limit or prevent leakage of fluid into the fallopian tubes.   
     
     
         62 . The system of  claim 61 , wherein the controller is programmed to control the flow of fluid supply such that it does not exceed a maximum pressure of the device of between about 2 ounces per square inch and 50 pounds of pressure per square inch. 
     
     
         63 . The system of  claim 61 , wherein the controller is programmed to control the flow of fluid supply such that it does not exceed a maximum pressure of the device of between about 2 ounces per square inch and 20 pounds of pressure per square inch. 
     
     
         64 . The system of  claim 61 , wherein the controller is programmed to control the delivery of the fluid through the fluid delivery and collection device into the uterus in a series of pulses at a pre-determined pulse rate. 
     
     
         65 . The system of  claim 64 , wherein the pulse rate has a preset frequency in the range of one pulse per 0.5 to 4 seconds. 
     
     
         66 . A uterine lavage system comprising:
 a fluid delivery and collection device; and   a controller programmed to deliver lavage liquid to the uterus from the device to assist with the recovery of blastocysts from the uterus and to apply vacuum pressure to the fluid to maintain the integrity of the blastocysts during fluid delivery and removal.   
     
     
         67 . The system of  claim 66 , wherein the vacuum pressure is between about 10 to 14 Hg. 
     
     
         68 . The system of  claim 67 , wherein the controller is programmed to control the withdrawal of the fluid through the fluid delivery and collection device from the uterus in a series of vacuum pulses at a pre-determined pulse rate. 
     
     
         69 . A uterine lavage system comprising:
 a fluid delivery and collection device; and   a controller programmed to both deliver lavage liquid to the uterus and apply vacuum to the fluid delivery and collection device, wherein the controller includes control logic which controls the fluid delivery and collection device so as to cause injecting a first small amount of fluid into the uterus to form a first puddle of fluid encompassing one or more blastocysts and to cause said first puddle of fluid to be suctioned into the device along with the one or more entrained blastocysts, and to inject at least one second amount of fluid into the uterus to form a second puddle which is larger than the first puddle and to suction the second puddle into the device along with one or more entrained blastocysts.   
     
     
         70 . The system of  claim 69 , wherein the controller is programmed to control the delivery of fluid through the fluid delivery and collection device such that the pressure of the fluid supply does not exceed a maximum pressure of the device of between about 2 ounces per square inch and 50 pounds of pressure per square inch to limit or prevent leakage of fluid into the fallopian tubes. 
     
     
         71 . The system of  claim 69 , wherein the controller is programmed to control the delivery of fluid through the fluid delivery and collection device such that the pressure of the fluid supply does not exceed a maximum pressure of the device of between about 2 ounces per square inch and 20 pounds of pressure per square inch to limit or prevent leakage of fluid into the fallopian tubes. 
     
     
         72 . The system of  claim 69 , wherein the controller is programmed to control the delivery of the fluid through the fluid delivery and collection device into the uterus in a series of pulses at a pre-determined pulse rate. 
     
     
         73 . The system of  claim 72 , wherein the pulse rate has a preset frequency in the range of one pulse per 0.5 to 4 seconds. 
     
     
         74 . The system of  claim 69 , wherein the controller is also programmed to control the withdrawal of the fluid through the fluid delivery and collection device from the uterus in a series of vacuum pulses at a pre-determined pulse rate. 
     
     
         75 . The system of  claim 74 , wherein the vacuum pressure is between about 10 to 14 Hg. 
     
     
         76 . A kit, comprising:
 a uterine lavage catheter configured for insertion into a woman's uterus to remove blastocysts from the uterus;   one or more first containers for storing one or more of a biopsied trophectoderm cells or inner cell mass recovered from the one or more blastocysts following a biopsy procedure to remove the one or more biopsied cells from the recovered blastocysts; and   one or more second containers for storing and cryopreserving the one or more of the recovered blastocysts following the biopsy procedure, wherein the one or more first and second containers each comprise one or more labels for identifying the one or more biopsied cells and the blastocyst from which said one or more biopsied cells was removed.   
     
     
         77 . The kit according to  claim 76 , further comprising one or more third containers comprising a sufficient dosage amount of a GnRH antagonist to cause corpus luteum apoptosis leading to desynchronization of the endometrium of the patient prior to, during and/or following recovery of blastocysts from the uterus. 
     
     
         78 . The kit according to  claim 76 , wherein the one or more second containers comprises one or more vials. 
     
     
         79 . The kit according to  claim 76 , wherein the one or more first containers comprises an electronic or other coding label including the biopsied cells and blastocyst identification information. 
     
     
         80 . The kit according to  claim 79 , wherein the one or more second containers comprises an electronic or other coding label including the biopsied cells and blastocyst identification information. 
     
     
         81 . The kit according to  claim 76 , further comprising at least one instrument or agent for performing a biopsy procedure to remove trophectoderm cells or inner cell mass from the one or more recovered blastocysts. 
     
     
         82 . The kit according to  claim 81 , wherein the at least one tool instrument comprises a holding instrument to stabilize one or more of the recovered blastocyst during the biopsy procedure. 
     
     
         83 . The kit according to  claim 81 , wherein the at least one instrument comprises a micropipette. 
     
     
         84 . The kit according to  claim 81 , wherein the at least one instrument comprises a control kit to ensure there is no contamination in the biopsied cells. 
     
     
         85 . The kit according to  claim 76 , further comprising instructions for use for processing and handling the biopsied cells. 
     
     
         86 . The kit according to  claim 76 , further comprising instructions for use for performing at least one molecular diagnostic assay test on the biopsied cells. 
     
     
         87 . The kit according to  claim 86 , wherein the at least one molecular diagnostic test comprises molecular diagnosis of Down syndrome. 
     
     
         88 . The kit according to  claim 86 , further comprising instructions for use for therapeutic embryonic intervention using selective replacement or gene therapy with specific corrective genetic constructs, specific non-genetic constructs, or stem cell/embryonic cell transplants following the at least one molecular diagnostic assay test. 
     
     
         89 . The kit according to  claim 88 , further comprising instructions for use for inserting the therapeutically treated embryo into the woman's uterus following said embryonic intervention. 
     
     
         90 . The kit according to  claim 86 , further comprising one or more reagents comprising nucleotide sequences capable of hybridizing with known chromosomal abnormalities. 
     
     
         91 . The kit according to  claim 90 , further comprising a microarray and/or a gene chip which is configured to hybridize with said chromosomal abnormalities, single gene mutations, corresponding normal sequences and/or sequences neighboring the chromosomal abnormalities.